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Rare anaemia v0.41 CUBN Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Rare anaemia v0.41 CUBN Louise Daugherty Gene: cubn has been classified as Green List (High Evidence).
Rare anaemia v0.40 CUBN Louise Daugherty commented on gene: CUBN: Discrepant reviews, to be discussed at July workshop to agree rating.
Rare anaemia v0.40 COX4I2 Louise Daugherty Classified gene: COX4I2 as Green List (high evidence)
Rare anaemia v0.40 COX4I2 Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Rare anaemia v0.40 COX4I2 Louise Daugherty Gene: cox4i2 has been classified as Green List (High Evidence).
Rare anaemia v0.39 COX4I2 Louise Daugherty commented on gene: COX4I2: Discrepant reviews, to be discussed at July workshop to agree rating.
Rare anaemia v0.39 AMN Louise Daugherty Classified gene: AMN as Green List (high evidence)
Rare anaemia v0.39 AMN Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Rare anaemia v0.39 AMN Louise Daugherty Gene: amn has been classified as Green List (High Evidence).
Rare anaemia v0.38 AMN Louise Daugherty commented on gene: AMN: Discrepant reviews, to be discussed at July workshop to agree rating.
Rare anaemia v0.38 AK1 Louise Daugherty Classified gene: AK1 as Green List (high evidence)
Rare anaemia v0.38 AK1 Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Rare anaemia v0.38 AK1 Louise Daugherty Gene: ak1 has been classified as Green List (High Evidence).
Rare anaemia v0.37 AK1 Louise Daugherty commented on gene: AK1: Discrepant reviews, to be discussed at July workshop to agree rating.
Rare anaemia v0.37 LPIN2 Louise Daugherty Classified gene: LPIN2 as Green List (high evidence)
Rare anaemia v0.37 LPIN2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Green
Rare anaemia v0.37 LPIN2 Louise Daugherty Gene: lpin2 has been classified as Green List (High Evidence).
Rare anaemia v0.36 LPIN2 Louise Daugherty commented on gene: LPIN2: Discrepant reviews, to be discussed at July workshop to agree rating.
Iron metabolism disorders - NOT common HFE mutations v0.53 ATP7B Louise Daugherty Classified gene: ATP7B as Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v0.53 ATP7B Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Iron metabolism disorders - NOT common HFE mutations v0.53 ATP7B Louise Daugherty Gene: atp7b has been classified as Green List (High Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.52 ABCB7 Louise Daugherty Classified gene: ABCB7 as Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v0.52 ABCB7 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Iron metabolism disorders - NOT common HFE mutations v0.52 ABCB7 Louise Daugherty Gene: abcb7 has been classified as Green List (High Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.51 ALAS2 Louise Daugherty Classified gene: ALAS2 as Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v0.51 ALAS2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Iron metabolism disorders - NOT common HFE mutations v0.51 ALAS2 Louise Daugherty Gene: alas2 has been classified as Green List (High Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.50 GLRX5 Louise Daugherty Classified gene: GLRX5 as Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v0.50 GLRX5 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Iron metabolism disorders - NOT common HFE mutations v0.50 GLRX5 Louise Daugherty Gene: glrx5 has been classified as Green List (High Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.49 SLC25A38 Louise Daugherty Classified gene: SLC25A38 as Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v0.49 SLC25A38 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Iron metabolism disorders - NOT common HFE mutations v0.49 SLC25A38 Louise Daugherty Gene: slc25a38 has been classified as Green List (High Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.48 FECH Louise Daugherty Classified gene: FECH as Amber List (moderate evidence)
Iron metabolism disorders - NOT common HFE mutations v0.48 FECH Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.
Iron metabolism disorders - NOT common HFE mutations v0.48 FECH Louise Daugherty Gene: fech has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.47 SERPINA1 Louise Daugherty Classified gene: SERPINA1 as Red List (low evidence)
Iron metabolism disorders - NOT common HFE mutations v0.47 SERPINA1 Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Red. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Red.
Iron metabolism disorders - NOT common HFE mutations v0.47 SERPINA1 Louise Daugherty Gene: serpina1 has been classified as Red List (Low Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.46 HEPH Louise Daugherty changed review comment from: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.; to: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.

Discrepant reviews, to be discussed at July workshop to agree rating.
Iron metabolism disorders - NOT common HFE mutations v0.46 HEPH Louise Daugherty Classified gene: HEPH as Amber List (moderate evidence)
Iron metabolism disorders - NOT common HFE mutations v0.46 HEPH Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.
Iron metabolism disorders - NOT common HFE mutations v0.46 HEPH Louise Daugherty Gene: heph has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.45 SEC23B Louise Daugherty Classified gene: SEC23B as Red List (low evidence)
Iron metabolism disorders - NOT common HFE mutations v0.45 SEC23B Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Red. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Red. It is Green on the rare anaemias panel
Iron metabolism disorders - NOT common HFE mutations v0.45 SEC23B Louise Daugherty Gene: sec23b has been classified as Red List (Low Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.44 FTH1 Louise Daugherty changed review comment from: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.; to: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.
Iron metabolism disorders - NOT common HFE mutations v0.44 CDAN1 Louise Daugherty Classified gene: CDAN1 as Red List (low evidence)
Iron metabolism disorders - NOT common HFE mutations v0.44 CDAN1 Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Red. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Red. YNEGLH noted that it is Green on the Rare Anaemia panel.
Iron metabolism disorders - NOT common HFE mutations v0.44 CDAN1 Louise Daugherty Gene: cdan1 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v1.178 ALKBH8 Catherine Snow edited their review of gene: ALKBH8: Changed rating: GREEN
Iron metabolism disorders - NOT common HFE mutations v0.43 CDAN1 Louise Daugherty commented on gene: CDAN1: Discrepant reviews, to be discussed at July workshop to agree rating.
Early onset or syndromic epilepsy v1.178 ALKBH8 Catherine Snow changed review comment from: Expert review by Konstantinos Varvagiannis on ALKBH8. Monies et al. (2019 - PMID: 31079898) report on 7 individuals from 2 different consanguineous Saudi families, harboring homozygous truncating ALKBH8 pathogenic variants. The same individuals are included in another concurrent publication from the same group (Monies et al. 2019 - PMID: 31130284).

Epilepsy was reported for 6/7 individuals although the type has not been commented on (onset 9-12 months to 2 years). Variable other phenotype features were noted in few.

ALKBH8 is not currently associated with any phenotype in OMIM / G2P.


ALKBH8 can be included in the epilepsy panel as Amber awaiting further evidence and tagged on the watchlist.; to: ALKBH8 had been identified by Genomic England curator when article was in press. Requested clinical team for support on rating on ID panel, clinical team advised "there are 7 affected individuals from two families with different LOF variants. They all have ID / GDD. There has been some functional work to indicate a lack of gene function in support. On balance I think this just meets our criteria for a green rating. 6/7 had seizures too so probably worth adding there too."
Iron metabolism disorders - NOT common HFE mutations v0.43 FTH1 Louise Daugherty Classified gene: FTH1 as Amber List (moderate evidence)
Iron metabolism disorders - NOT common HFE mutations v0.43 FTH1 Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.
Iron metabolism disorders - NOT common HFE mutations v0.43 FTH1 Louise Daugherty Gene: fth1 has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v0.42 FTH1 Louise Daugherty commented on gene: FTH1: Discrepant reviews, to be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.118 TP53 Louise Daugherty Classified gene: TP53 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.118 TP53 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH the gene is associated with breast cancer rather than cytopenia
Cytopenia - NOT Fanconi anaemia v0.118 TP53 Louise Daugherty Gene: tp53 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.117 STIM1 Louise Daugherty Classified gene: STIM1 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.117 STIM1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH as being Green on the Bleeding and Platelet disorders panel but should be Red on this panel
Cytopenia - NOT Fanconi anaemia v0.117 STIM1 Louise Daugherty Gene: stim1 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.116 SMARCAL1 Louise Daugherty Classified gene: SMARCAL1 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.116 SMARCAL1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH as syndromic
Cytopenia - NOT Fanconi anaemia v0.116 SMARCAL1 Louise Daugherty Gene: smarcal1 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.115 SLC37A4 Louise Daugherty Classified gene: SLC37A4 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.115 SLC37A4 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH - other discipline (IEM-GSD) so should be Red on this panel
Cytopenia - NOT Fanconi anaemia v0.115 SLC37A4 Louise Daugherty Gene: slc37a4 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.114 RUNX1 Louise Daugherty Classified gene: RUNX1 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.114 RUNX1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH the gene is rated Green on the R90 Bleeding and platelet disorders panel and AML panel but should be Red for R91 Cytopenia - NOT Fanconi anaemia panel
Cytopenia - NOT Fanconi anaemia v0.114 RUNX1 Louise Daugherty Gene: runx1 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.113 RPS27 Louise Daugherty Classified gene: RPS27 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.113 RPS27 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH the gene is rated Green on the R92 Rare anaemia panel but should be Red for R91 Cytopenia - NOT Fanconi anaemia panel
Cytopenia - NOT Fanconi anaemia v0.113 RPS27 Louise Daugherty Gene: rps27 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.112 RPS27 Louise Daugherty Deleted their comment
Cytopenia - NOT Fanconi anaemia v0.112 NBEAL2 Louise Daugherty changed review comment from: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red.; to: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH the gene is rated Green on the R90 Bleeding and platelet disorders panel but should be Red for R91 Cytopenia - NOT Fanconi anaemia panel
Cytopenia - NOT Fanconi anaemia v0.112 MYH9 Louise Daugherty changed review comment from: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red.; to: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH the gene is rated Green on the R90 Bleeding and platelet disorders panel but should be Red for R91 Cytopenia - NOT Fanconi anaemia panel
Cytopenia - NOT Fanconi anaemia v0.112 NBEAL2 Louise Daugherty Classified gene: NBEAL2 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.112 NBEAL2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red.
Cytopenia - NOT Fanconi anaemia v0.112 NBEAL2 Louise Daugherty Gene: nbeal2 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.111 MYH9 Louise Daugherty Classified gene: MYH9 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.111 MYH9 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red.
Cytopenia - NOT Fanconi anaemia v0.111 MYH9 Louise Daugherty Gene: myh9 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.110 LIG4 Louise Daugherty Classified gene: LIG4 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.110 LIG4 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. YNEGLH noted it was syndromic.
Cytopenia - NOT Fanconi anaemia v0.110 LIG4 Louise Daugherty Gene: lig4 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.109 GP1BA Louise Daugherty Classified gene: GP1BA as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.109 GP1BA Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. Noted by YNEGLH the gene is rated Green on the R90 Bleeding and platelet disorders panel but should be red for R91 Cytopenia - NOT Fanconi anaemia panel
Cytopenia - NOT Fanconi anaemia v0.109 GP1BA Louise Daugherty Gene: gp1ba has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.108 DDX41 Louise Daugherty Classified gene: DDX41 as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v0.108 DDX41 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be downgraded from Green to Red. YNEGLH noted this is a susceptibility gene.
Cytopenia - NOT Fanconi anaemia v0.108 DDX41 Louise Daugherty Gene: ddx41 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v0.107 USB1 Louise Daugherty Mode of inheritance for gene: USB1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v0.106 RPL31 Louise Daugherty Mode of inheritance for gene: RPL31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenia - NOT Fanconi anaemia v0.105 RPL27 Louise Daugherty Mode of inheritance for gene: RPL27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenia - NOT Fanconi anaemia v0.104 ADA2 Louise Daugherty Mode of inheritance for gene: ADA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.177 KCNH5 Catherine Snow Source Expert Review Red was added to KCNH5.
Mode of inheritance for gene KCNH5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes epilepsy for gene: KCNH5
Rating Changed from No List (delete) to Red List (low evidence)
Early onset or syndromic epilepsy v1.177 KCND2 Catherine Snow Source Expert Review Red was added to KCND2.
Mode of inheritance for gene KCND2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of pathogenicity for gene KCND2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes epilepsy; autism for gene: KCND2
Rating Changed from No List (delete) to Red List (low evidence)
Early onset or syndromic epilepsy v1.177 ZNF142 Catherine Snow Source Expert Review was added to ZNF142.
Source Expert Review Amber was added to ZNF142.
Added phenotypes Neurodevelopmental disorder with impaired speech and hyperkinetic movements, 618425 for gene: ZNF142
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.177 ZMIZ1 Catherine Snow Source Expert Review was added to ZMIZ1.
Source Expert Review Amber was added to ZMIZ1.
Publications for gene ZMIZ1 were changed from 29754769; 18053775; 17967885; 26163108; 27479843 to 18053775; 27479843; 29754769; 17967885; 26163108
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.177 TRRAP Catherine Snow Source Expert Review was added to TRRAP.
Source Expert Review Amber was added to TRRAP.
Added phenotypes Developmental delay with or without dysmorphic facies and autism, 603015 for gene: TRRAP
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.177 RNF13 Catherine Snow Source Expert Review was added to RNF13.
Source Expert Review Amber was added to RNF13.
Added phenotypes Epileptic encephalopathy, early infantile, 73 for gene: RNF13
Publications for gene RNF13 were changed from to 30595371
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.177 LSS Catherine Snow Source Expert Review was added to LSS.
Source Expert Review Amber was added to LSS.
Added phenotypes Cataract 44, 616509, Hypotrichosis 14, 618275 for gene: LSS
Publications for gene LSS were changed from 30723320 to 30723320; 26200341; 30401459; 29016354
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.177 FUK Catherine Snow Source Expert Review was added to FUK.
Source Expert Review Amber was added to FUK.
Added phenotypes Congenital disorder of glycosylation with defective fucosylation 2, 618324 for gene: FUK
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.177 ZDHHC9 Catherine Snow Source Expert Review Green was added to ZDHHC9.
Source Expert Review was added to ZDHHC9.
Added phenotypes Mental retardation, X-linked syndromic, Raymond type, 300799 for gene: ZDHHC9
Publications for gene ZDHHC9 were changed from 26000327 to 24357419; 26000327; 29681091
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 WARS2 Catherine Snow Source Expert Review Green was added to WARS2.
Source Expert Review was added to WARS2.
Added phenotypes Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, 617710 for gene: WARS2
Publications for gene WARS2 were changed from 28236339; 28650581; 28905505; 29783990; 29120065 to 29783990; 28236339; 29120065; 28650581; 28905505
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 VPS11 Catherine Snow Source Expert Review Green was added to VPS11.
Source Expert Review was added to VPS11.
Added phenotypes Leukodystrophy, hypomyelinating, 12 for gene: VPS11
Publications for gene VPS11 were changed from 27120463; 26307567; 27473128 to 27473128; 26307567; 27120463
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 VAMP2 Catherine Snow Source Expert Review Green was added to VAMP2.
Source Expert Review was added to VAMP2.
Added phenotypes Generalized hypotonia, Global developmental delay, Intellectual disability, Autistic behavior, Stereotypic behavior, Seizures, Abnormality of movement, Cortical visual impairment for gene: VAMP2
Publications for gene VAMP2 were changed from 30929742 to 27458546; 22183055; 30929742
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 SNAP25 Catherine Snow Source Expert Review Green was added to SNAP25.
Source Expert Review was added to SNAP25.
Added phenotypes ?Myasthenic syndrome, congenital, 18 for gene: SNAP25
Publications for gene SNAP25 were changed from 29491473; 28135719; 29100083; 25381298; 25003006 to 29100083; 28135719; 25003006; 29491473; 25381298; 30914295
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 PPP2CA Catherine Snow Source Expert Review Green was added to PPP2CA.
Source Expert Review was added to PPP2CA.
Added phenotypes Neurodevelopmental disorder and language delay with or without structural brain abnormalities, 618354 for gene: PPP2CA
Publications for gene PPP2CA were changed from 29274472; 30030003 to 29274472; 30030003; 30595372
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 P4HTM Catherine Snow Source Expert Review Green was added to P4HTM.
Source Expert Review was added to P4HTM.
Added phenotypes Abnormality of the eye; Seizures; Dysautonomia; Central hypotonia; Muscular hypotonia; Hypoventilation; Intellectual disability; Sleep apnea; Global developmental delay for gene: P4HTM
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 KCNT2 Catherine Snow Source Expert Review Green was added to KCNT2.
Source Expert Review was added to KCNT2.
Mode of inheritance for gene KCNT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes ?Epileptic encephalopathy, early infantile, 57 for gene: KCNT2
Publications for gene KCNT2 were changed from 29740868; 29069600 to 29069600; 29740868
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 DHPS Catherine Snow Source Expert Review Green was added to DHPS.
Source Expert Review was added to DHPS.
Added phenotypes Abnormality of head or neck; Seizures; EEG abnormality; Behavioral abnormality; Abnormal muscle tone; Intellectual disability; Global developmental delay for gene: DHPS
Publications for gene DHPS were changed from 21389784; 21850436 to 21389784; 30661771; 21850436
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 ATN1 Catherine Snow Source Expert Review Green was added to ATN1.
Source Expert Review was added to ATN1.
Added phenotypes Hypotonia; Epilepsy; Digit Abnormalities; Developmental Delay for gene: ATN1
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 AP2M1 Catherine Snow Source Expert Review Green was added to AP2M1.
Source Expert Review was added to AP2M1.
Mode of pathogenicity for gene AP2M1 was changed from None to Other
Added phenotypes Seizures; Ataxia; Generalized hypotonia; Intellectual disability; Global developmental delay; Autistic behavior for gene: AP2M1
Rating Changed from No List (delete) to Green List (high evidence)
Early onset or syndromic epilepsy v1.177 ALKBH8 Catherine Snow Source Expert Review Green was added to ALKBH8.
Source Expert Review was added to ALKBH8.
Added phenotypes Seizures; Developmental Delay; Intellectual Disability for gene: ALKBH8
Publications for gene ALKBH8 were changed from 31079898 to 31130284; 31079898
Rating Changed from No List (delete) to Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.103 ADA2 Louise Daugherty Classified gene: ADA2 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.103 ADA2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.103 ADA2 Louise Daugherty Gene: ada2 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.102 RPS7 Louise Daugherty Classified gene: RPS7 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.102 RPS7 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.102 RPS7 Louise Daugherty Gene: rps7 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.101 RPS27 Louise Daugherty Classified gene: RPS27 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.101 RPS27 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.101 RPS27 Louise Daugherty Gene: rps27 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.100 RPS26 Louise Daugherty Classified gene: RPS26 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.100 RPS26 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.100 RPS26 Louise Daugherty Gene: rps26 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.99 RPS24 Louise Daugherty Classified gene: RPS24 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.99 RPS24 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.99 RPS24 Louise Daugherty Gene: rps24 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.98 RPS19 Louise Daugherty Classified gene: RPS19 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.98 RPS19 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.98 RPS19 Louise Daugherty Gene: rps19 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.97 RPS17 Louise Daugherty Classified gene: RPS17 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.97 RPS17 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.97 RPS17 Louise Daugherty Gene: rps17 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.96 RPS10 Louise Daugherty Classified gene: RPS10 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.96 RPS10 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.96 RPS10 Louise Daugherty Gene: rps10 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.95 RPL9 Louise Daugherty Classified gene: RPL9 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.95 RPL9 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.95 RPL9 Louise Daugherty Gene: rpl9 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.94 RPL5 Louise Daugherty Classified gene: RPL5 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.94 RPL5 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.94 RPL5 Louise Daugherty Gene: rpl5 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.93 RPL35A Louise Daugherty Classified gene: RPL35A as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.93 RPL35A Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.93 RPL35A Louise Daugherty Gene: rpl35a has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.92 RPL31 Louise Daugherty Classified gene: RPL31 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.92 RPL31 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.92 RPL31 Louise Daugherty Gene: rpl31 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.91 RPS29 Louise Daugherty Classified gene: RPS29 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.91 RPS29 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.91 RPS29 Louise Daugherty Gene: rps29 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.90 RPL27 Louise Daugherty Classified gene: RPL27 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.90 RPL27 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.90 RPL27 Louise Daugherty Gene: rpl27 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.89 RPL26 Louise Daugherty Classified gene: RPL26 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.89 RPL26 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.89 RPL26 Louise Daugherty Gene: rpl26 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.88 RPL15 Louise Daugherty Classified gene: RPL15 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.88 RPL15 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.88 RPL15 Louise Daugherty Gene: rpl15 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.87 RPL11 Louise Daugherty Classified gene: RPL11 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.87 RPL11 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.87 RPL11 Louise Daugherty Gene: rpl11 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy Super panel v0.0 Ellen McDonagh Added Panel Rare multisystem ciliopathy Super panel
Set child panels to: Respiratory ciliopathies including non-CF bronchiectasis; Skeletal ciliopathies; Ophthalmological ciliopathies; Renal ciliopathies; Neurological ciliopathies
Set panel types to: Rare Disease 100K; Super Panel
Cytopenia - NOT Fanconi anaemia v0.86 WIPF1 Louise Daugherty Classified gene: WIPF1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.86 WIPF1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.86 WIPF1 Louise Daugherty Gene: wipf1 has been classified as Green List (High Evidence).
Ophthalmological ciliopathies v0.7 Ellen McDonagh Panel status changed from internal to public
Neurological ciliopathies v0.1 Ellen McDonagh Panel status changed from internal to public
Cytopenia - NOT Fanconi anaemia v0.85 KLF1 Louise Daugherty Classified gene: KLF1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.85 KLF1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.85 KLF1 Louise Daugherty Gene: klf1 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.84 KIF23 Louise Daugherty Classified gene: KIF23 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.84 KIF23 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.84 KIF23 Louise Daugherty Gene: kif23 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.83 RMRP Louise Daugherty Classified gene: RMRP as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.83 RMRP Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.83 RMRP Louise Daugherty Gene: rmrp has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.82 ETV6 Louise Daugherty Classified gene: ETV6 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.82 ETV6 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.82 ETV6 Louise Daugherty Gene: etv6 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.81 ANKRD26 Louise Daugherty Classified gene: ANKRD26 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.81 ANKRD26 Louise Daugherty Added comment: Comment on list classification: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.81 ANKRD26 Louise Daugherty Gene: ankrd26 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.80 CYCS Louise Daugherty Classified gene: CYCS as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.80 CYCS Louise Daugherty Added comment: Comment on list classification: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.80 CYCS Louise Daugherty Gene: cycs has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.79 MPL Louise Daugherty Classified gene: MPL as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.79 MPL Louise Daugherty Added comment: Comment on list classification: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.79 MPL Louise Daugherty Gene: mpl has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.78 MECOM Louise Daugherty Classified gene: MECOM as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.78 MECOM Louise Daugherty Added comment: Comment on list classification: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.78 MECOM Louise Daugherty Gene: mecom has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.77 ACD Louise Daugherty changed review comment from: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that there is enough evidence to rate this gene Green.; to: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.77 PARN Louise Daugherty changed review comment from: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that there is enough evidence to rate this gene Green.; to: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.77 PARN Louise Daugherty Classified gene: PARN as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.77 PARN Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.77 PARN Louise Daugherty Gene: parn has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.76 ACD Louise Daugherty Classified gene: ACD as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.76 ACD Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.76 ACD Louise Daugherty Gene: acd has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.176 KIF1BP Rebecca Foulger commented on gene: KIF1BP
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty changed review comment from: Discrepant reviews for NOP10. To be discussed at July workshop to agree rating

Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.; to: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.

Discrepant reviews for NOP10. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty changed review comment from: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.; to: Discrepant reviews for NOP10. To be discussed at July workshop to agree rating

Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty Deleted their comment
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty changed review comment from: Discrepant reviews for NOP10. To be discussed at July workshop to agree rating; to: Discrepant reviews for NOP10. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty commented on gene: NOP10: Discrepant reviews for NOP10. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty Classified gene: NOP10 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.75 NOP10 Louise Daugherty Gene: nop10 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.74 NHP2 Louise Daugherty Classified gene: NHP2 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.74 NHP2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.74 NHP2 Louise Daugherty Gene: nhp2 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.73 NHP2 Louise Daugherty commented on gene: NHP2: Discrepant reviews for NHP2. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.73 SRP72 Louise Daugherty Classified gene: SRP72 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.73 SRP72 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.73 SRP72 Louise Daugherty Gene: srp72 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.72 SRP72 Louise Daugherty commented on gene: SRP72: Discrepant reviews for SRP72. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.72 WRAP53 Louise Daugherty Classified gene: WRAP53 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.72 WRAP53 Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.72 WRAP53 Louise Daugherty Gene: wrap53 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.71 WRAP53 Louise Daugherty commented on gene: WRAP53: Discrepant reviews for WRAP53. Rated as Amber WWMGLH - Green rating LSGLH, YNEGLH, NWGLH. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.71 USB1 Louise Daugherty Classified gene: USB1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.71 USB1 Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.71 USB1 Louise Daugherty Gene: usb1 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.70 USB1 Louise Daugherty commented on gene: USB1: Discrepant reviews for USB. Rated as Amber WWMGLH - Green rating LSGLH, YNEGLH, NWGLH. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.70 TINF2 Louise Daugherty Classified gene: TINF2 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.70 TINF2 Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.70 TINF2 Louise Daugherty Gene: tinf2 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.69 TINF2 Louise Daugherty commented on gene: TINF2: Discrepant reviews forTINF2. Rated as Amber WWMGLH - Green rating LSGLH, YNEGLH, NWGLH. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.69 TERC Louise Daugherty Classified gene: TERC as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.69 TERC Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.69 TERC Louise Daugherty Gene: terc has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.68 TERC Louise Daugherty changed review comment from: RBM8A: Discrepant reviews for TERC. Rated as Amber WWMGLH - Green rating LSGLH, YNEGLH, NWGLH. To be discussed at July workshop to agree rating; to: Discrepant reviews for TERC. Rated as Amber WWMGLH - Green rating LSGLH, YNEGLH, NWGLH. To be discussed at July workshop to agree rating
Cytopenia - NOT Fanconi anaemia v0.68 TERC Louise Daugherty commented on gene: TERC: RBM8A: Discrepant reviews for TERC. Rated as Amber WWMGLH - Green rating LSGLH, YNEGLH, NWGLH. To be discussed at July workshop to agree rating
Early onset or syndromic epilepsy v1.176 FLNA Rebecca Foulger Publications for gene: FLNA were set to 15668422; 20014127; 25755106
Early onset or syndromic epilepsy v1.175 FLNA Rebecca Foulger Publications for gene: FLNA were set to
Early onset or syndromic epilepsy v1.174 FLNA Rebecca Foulger commented on gene: FLNA: PMID:25755106. In a woman and her 3 daughters with a complex phenotype comprising both periventricular nodular heterotopia and Melnick-Needles syndrome, Parrini et al. (2015) identified a c.622G-C transversion in exon 3 of the FLNA gene (G208R). The 3 daughters had onset of seizures in the first decade.
Early onset or syndromic epilepsy v1.174 FLNA Rebecca Foulger commented on gene: FLNA: PMID:20014127. In an 18-month-old girl with periventricular nodular heterotopia and seizures, Jefferies et al. (2010) identified a heterozygous 7896G-A transition in the FLNA gene (W2632X).
Early onset or syndromic epilepsy v1.174 FLNA Rebecca Foulger commented on gene: FLNA
Cytopenia - NOT Fanconi anaemia v0.68 JAGN1 Louise Daugherty Classified gene: JAGN1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.68 JAGN1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.68 JAGN1 Louise Daugherty Gene: jagn1 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.67 RBM8A Louise Daugherty Classified gene: RBM8A as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.67 RBM8A Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.67 RBM8A Louise Daugherty Gene: rbm8a has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.66 RBM8A Louise Daugherty commented on gene: RBM8A: Discrepant reviews for RBM8A. Rated as Green by LSGLH, YNEGLH - Amber rating by NWGLH, no review WWMGLH. To be discussed at July workshop to agree rating
Early onset or syndromic epilepsy v1.174 FGFR3 Rebecca Foulger Publications for gene: FGFR3 were set to 27485793; 23649205; 24630288; 17621485; 16222682; 12794698; 23044018; 12794698; 18000976; http://doi.org/10.15844/pedneurbriefs-26-12-6; http://www.ashg.org/genetics/ashg07s/f20570.htm; https://jicna.org/index.php/journal/article/view/100
Early onset or syndromic epilepsy v1.173 FGFR3 Rebecca Foulger commented on gene: FGFR3
Early onset or syndromic epilepsy v1.173 EMX2 Rebecca Foulger changed review comment from: Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have EMX2 variants (patients VF, MB and PB).; to: Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Cytopenia - NOT Fanconi anaemia v0.66 NBN Louise Daugherty changed review comment from: Discrepant reviews for NBN:Rated as Green by WWMGLH, NWGLH - Amber rating by YNEGLH, LSGLH. To be discussed at July workshop to agree rating.; to: Discrepant reviews for NBN:Rated as Green by WWMGLH, NWGLH - Amber rating by YNEGLH, LSGLH. To be discussed at July workshop to agree rating. As noted by LSGLH -not sure if this should be in Cytopenia panel – would this not be picked up on chromosome breakage? Then better to go for the single gene test R259.
Cytopenia - NOT Fanconi anaemia v0.66 NBN Louise Daugherty Classified gene: NBN as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.66 NBN Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.66 NBN Louise Daugherty Gene: nbn has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.65 NBN Louise Daugherty commented on gene: NBN: Discrepant reviews for NBN:Rated as Green by WWMGLH, NWGLH - Amber rating by YNEGLH, LSGLH. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.65 JAGN1 Louise Daugherty commented on gene: JAGN1: Discrepant reviews for JAGN1 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.65 TERT Louise Daugherty Classified gene: TERT as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.65 TERT Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.65 TERT Louise Daugherty Gene: tert has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.64 TERT Louise Daugherty commented on gene: TERT: Discrepant reviews for TERT : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.64 GATA2 Louise Daugherty Classified gene: GATA2 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.64 GATA2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.64 GATA2 Louise Daugherty Gene: gata2 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.63 GATA2 Louise Daugherty commented on gene: GATA2: Discrepant reviews for GATA2 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.63 GATA1 Louise Daugherty Classified gene: GATA1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.63 GATA1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.63 GATA1 Louise Daugherty Gene: gata1 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.62 GATA1 Louise Daugherty commented on gene: GATA1: Discrepant reviews for GATA1 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.62 FYB1 Louise Daugherty Classified gene: FYB1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.62 FYB1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.62 FYB1 Louise Daugherty Gene: fyb1 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.61 FYB1 Louise Daugherty commented on gene: FYB1: Discrepant reviews for FYB1. Rated as Green by YNEGLH, LSGLH - Amber rating by NWGLH, no review by WWMGLH. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.61 EFL1 Louise Daugherty changed review comment from: Discrepant reviews for EFL1: Rated as Green by LSGLH, YNEGLH- Amber rating NWGLH, no review by WWMGLH. To be discussed at July workshop to agree rating.; to: Discrepant reviews for EFL1: Rated as Green by LSGLH, YNEGLH- Amber rating NWGLH, no review by WWMGLH. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.61 EFL1 Louise Daugherty Classified gene: EFL1 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v0.61 EFL1 Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Cytopenia - NOT Fanconi anaemia v0.61 EFL1 Louise Daugherty Gene: efl1 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v0.60 EFL1 Louise Daugherty commented on gene: EFL1: Discrepant reviews for EFL1: Rated as Green by LSGLH, YNEGLH- Amber rating NWGLH, no review by WWMGLH. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.60 CXCR4 Louise Daugherty Classified gene: CXCR4 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.60 CXCR4 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.60 CXCR4 Louise Daugherty Gene: cxcr4 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.59 CXCR4 Louise Daugherty commented on gene: CXCR4: Discrepant reviews for CXCR4 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Cytopenia - NOT Fanconi anaemia v0.59 CTC1 Louise Daugherty Classified gene: CTC1 as Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v0.59 CTC1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Cytopenia - NOT Fanconi anaemia v0.59 CTC1 Louise Daugherty Gene: ctc1 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v0.58 CTC1 Louise Daugherty commented on gene: CTC1: Discrepant reviews for CTC1 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Early onset or syndromic epilepsy v1.173 DHCR7 Rebecca Foulger commented on gene: DHCR7: PMID:29226552: Dang Do et al., 2018 report 3 individuals with SLOS- seizures seen in 1 of 3 patients.
Early onset or syndromic epilepsy v1.173 DHCR7 Rebecca Foulger commented on gene: DHCR7: PMID:10807690: Kelley et al., 2000 report that seizures are uncommon in biochemically-proven cases of Smith-Lemli-Poitz syndrome (SLOS), and may not be substantially more frequent than in children without SLOS.
Early onset or syndromic epilepsy v1.173 DHCR7 Rebecca Foulger commented on gene: DHCR7
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty changed review comment from: Discrepant reviews for RAD51C : 1 GLH GREEN (YNEGLH), 3 GLH AMBER (WWMGLH, NWGLH, LSGLH). To be discussed at July workshop to agree rating.; to: Discrepant reviews for RAD51C : 1 GLH GREEN (YNEGLH), 3 GLH AMBER (WWMGLH, NWGLH, LSGLH). To be discussed at July workshop to agree rating.
NWGLH: GREEN/AMBER – would go with the consensus
LSGLH: AMBER – one family reported
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty Classified gene: RAD51C as Amber List (moderate evidence)
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty Gene: rad51c has been classified as Amber List (Moderate Evidence).
Confirmed Fanconi anaemia or Bloom syndrome v0.26 RAD51C Louise Daugherty commented on gene: RAD51C: Discrepant reviews for RAD51C : 1 GLH GREEN (YNEGLH), 3 GLH AMBER (WWMGLH, NWGLH, LSGLH). To be discussed at July workshop to agree rating.
Confirmed Fanconi anaemia or Bloom syndrome v0.26 FANCM Louise Daugherty Classified gene: FANCM as Red List (low evidence)
Confirmed Fanconi anaemia or Bloom syndrome v0.26 FANCM Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Red
Confirmed Fanconi anaemia or Bloom syndrome v0.26 FANCM Louise Daugherty Gene: fancm has been classified as Red List (Low Evidence).
Confirmed Fanconi anaemia or Bloom syndrome v0.25 FANCM Louise Daugherty changed review comment from: Discrepant reviews for FANCM: 2 GLH GREEN (YNEGLH, NWGLH), 2 GLH RED (LSGLH, WWMGLH). To be discussed at July workshop to agree rating.
LSGLH: see Genet Med. 2018 Apr;20(4):452-457. doi: 10.1038/gim.2017.123. Epub 2017 Aug 24. Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility; to: Discrepant reviews for FANCM: 2 GLH GREEN (YNEGLH, NWGLH), 2 GLH RED (LSGLH, WWMGLH). To be discussed at July workshop to agree rating.
LSGLH: see Genet Med. 2018 Apr;20(4):452-457. doi: 10.1038/gim.2017.123. Epub 2017 Aug 24 (PMID: 28837162 ). Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility
Confirmed Fanconi anaemia or Bloom syndrome v0.25 FANCM Louise Daugherty Publications for gene: FANCM were set to 19423727; 25078778; 16116422
Confirmed Fanconi anaemia or Bloom syndrome v0.24 FANCM Louise Daugherty changed review comment from: Discrepant reviews for FANCM: 2 GLH GREEN (YNEGLH, NWGLH), 2 GLH RED (LSGLH, WWMGLH). To be discussed at July workshop to agree rating.; to: Discrepant reviews for FANCM: 2 GLH GREEN (YNEGLH, NWGLH), 2 GLH RED (LSGLH, WWMGLH). To be discussed at July workshop to agree rating.
LSGLH: see Genet Med. 2018 Apr;20(4):452-457. doi: 10.1038/gim.2017.123. Epub 2017 Aug 24. Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility
Confirmed Fanconi anaemia or Bloom syndrome v0.24 FANCM Louise Daugherty commented on gene: FANCM: Discrepant reviews for FANCM: 2 GLH GREEN (YNEGLH, NWGLH), 2 GLH RED (LSGLH, WWMGLH). To be discussed at July workshop to agree rating.
Early onset or syndromic epilepsy v1.173 ALPL Rebecca Foulger Publications for gene: ALPL were set to 11999978; 28802630; 23479201; 27086862; 30655187; 30083035
Early onset or syndromic epilepsy v1.172 ALPL Rebecca Foulger commented on gene: ALPL: PMID:30979546: Whyte et al., 2019 report Vitamin B6-dependent seizures in 10/38 (26%) of patients: 7 patients had documented seizures and 3 patients had a family hisotry of seizures based upon medical records.
Confirmed Fanconi anaemia or Bloom syndrome v0.24 BRCA1 Louise Daugherty changed review comment from: Discrepant reviews for BRCA1 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.; to: Discrepant reviews for BRCA1 : 3 GLH GREEN (YNEGLH, NWGLH, LSGLH), 1 GLH AMBER (WWMGLH). To be discussed at July workshop to agree rating.
Confirmed Fanconi anaemia or Bloom syndrome v0.24 BRCA1 Louise Daugherty Classified gene: BRCA1 as Green List (high evidence)
Confirmed Fanconi anaemia or Bloom syndrome v0.24 BRCA1 Louise Daugherty Added comment: Comment on list classification: Upgraded from Amber to Green. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is enough evidence to rate this gene Green.
Confirmed Fanconi anaemia or Bloom syndrome v0.24 BRCA1 Louise Daugherty Gene: brca1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.172 ALPL Rebecca Foulger commented on gene: ALPL: PMID:30083035: Oyachi et al., 2018 report a newborn girl with compound het variants in ALPL (c.1559delT/p.Ser188Pro). The patient had seizures on days 2-4, treated with pyridoxine.
Early onset or syndromic epilepsy v1.172 ALPL Rebecca Foulger commented on gene: ALPL: PMID:27086862 (2018) report a female infantile hypophosphatasia patient who presented with pyridoxine-responsive myoclonic seizures and a novel homozygous mutation in the ALPL gene(c.799_804delCACTTC). Parents were heterozygous for the variant.
Early onset or syndromic epilepsy v1.172 ALPL Rebecca Foulger Publications for gene: ALPL were set to 11999978; 28802630; 23479201
Confirmed Fanconi anaemia or Bloom syndrome v0.23 BRCA1 Louise Daugherty commented on gene: BRCA1: Discrepant reviews for BRCA1 : 3 GLH GREEN, 1 GLH AMBER. To be discussed at July workshop to agree rating.
Bleeding and platelet disorders v0.72 SMAD4 Louise Daugherty changed review comment from: GLH reviews since webex on 8th March 2019:
YNEGLH- Associated with a few syndromes all with cardiac problems- bleeding not mentioned in omim occasionally anaemia- RED
WWMGLH- SMAD 4 IS 1 OF THE GENES FOR HHT AMBER
NWGLH- categorise as AMBER
LSGLH – no association with bleeding phenotype – RED; to: GLH reviews since webex on 8th March 2019:
YNEGLH: Associated with a few syndromes all with cardiac problems- bleeding not mentioned in omim occasionally anaemia- RED
WWMGLH: SMAD 4 IS 1 OF THE GENES FOR HHT AMBER
NWGLH: categorise as AMBER
LSGLH: no association with bleeding phenotype – RED
Bleeding and platelet disorders v0.72 SMAD4 Louise Daugherty Classified gene: SMAD4 as Amber List (moderate evidence)
Bleeding and platelet disorders v0.72 SMAD4 Louise Daugherty Added comment: Comment on list classification: Upgraded rating from Red to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Bleeding and platelet disorders v0.72 SMAD4 Louise Daugherty Gene: smad4 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.71 SMAD4 Louise Daugherty commented on gene: SMAD4: GLH reviews since webex on 8th March 2019:
YNEGLH- Associated with a few syndromes all with cardiac problems- bleeding not mentioned in omim occasionally anaemia- RED
WWMGLH- SMAD 4 IS 1 OF THE GENES FOR HHT AMBER
NWGLH- categorise as AMBER
LSGLH – no association with bleeding phenotype – RED
Bleeding and platelet disorders v0.71 RNU4ATAC Louise Daugherty Classified gene: RNU4ATAC as Amber List (moderate evidence)
Bleeding and platelet disorders v0.71 RNU4ATAC Louise Daugherty Added comment: Comment on list classification: Downgraded rating from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Bleeding and platelet disorders v0.71 RNU4ATAC Louise Daugherty Gene: rnu4atac has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.70 RNU4ATAC Louise Daugherty changed review comment from: GLH reviews since webex on 8th March 2019:
YNEGLH- RNU4ATAC seems very syndromic and no bleeding association in HGMD- all changes associated with disease are in 5’ UTR- RED
WWMGLH- IT IS ON THE ISTH GENE LIST GREEN WWMGLH
NWGLH – this target is associated with pronounced syndromes so I would not include on R90
LSGLH- I’d agree that that gene is unlikely to present with isolated bleeding symptoms. Don’t think it should be included as Green. Happy for it to be AMBER or RED.; to: GLH reviews since webex on 8th March 2019:
YNEGLH- RNU4ATAC seems very syndromic and no bleeding association in HGMD- all changes associated with disease are in 5’ UTR- RED
WWMGLH- IT IS ON THE ISTH GENE LIST GREEN
NWGLH – this target is associated with pronounced syndromes so I would not include on R90
LSGLH- I’d agree that that gene is unlikely to present with isolated bleeding symptoms. Don’t think it should be included as Green. Happy for it to be AMBER or RED.
Bleeding and platelet disorders v0.70 RNU4ATAC Louise Daugherty commented on gene: RNU4ATAC: GLH reviews since webex on 8th March 2019:
YNEGLH- RNU4ATAC seems very syndromic and no bleeding association in HGMD- all changes associated with disease are in 5’ UTR- RED
WWMGLH- IT IS ON THE ISTH GENE LIST GREEN WWMGLH
NWGLH – this target is associated with pronounced syndromes so I would not include on R90
LSGLH- I’d agree that that gene is unlikely to present with isolated bleeding symptoms. Don’t think it should be included as Green. Happy for it to be AMBER or RED.
Bleeding and platelet disorders v0.70 COL5A2 Louise Daugherty commented on gene: COL5A2: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Bleeding and platelet disorders v0.70 COL5A1 Louise Daugherty commented on gene: COL5A1: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Bleeding and platelet disorders v0.70 COL1A1 Louise Daugherty commented on gene: COL1A1: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Bleeding and platelet disorders v0.70 COL3A1 Louise Daugherty Publications for gene: COL3A1 were set to 22019127; 25758994; 22143279
Bleeding and platelet disorders v0.69 COL3A1 Louise Daugherty commented on gene: COL3A1: Discussed further with the GMS Haematology Specialist Test Group at workshop 2nd July 2019, it was agreed that Carl Fratter would review the evidence on COL3A1 by contacting their Thrombogenomics team to ask if they are able to provide any information on their experience, as they have included these genes in their panel. Gene rating to be confirmed when group has this information.

Carl Fratter has since highlighted a report (PMID: 30690834) with a family with COL3A1 who presented with bruising (prepositus/family 3), noting it’s complicated by the fact that they are reporting it because of a VWF variant of uncertain significance (which is quite common in the general population, and so perhaps not likely to be very significant), but does appear to be an example of COL3A1 related EDS which was not obvious clinically and patient was referred for easy bruising before EDS was diagnosed. Awaiting consensus from the GMS Haematology Specialist Test Group regarding this
Bleeding and platelet disorders v0.69 CHST14 Louise Daugherty commented on gene: CHST14: Discussed further with the GMS Haematology Specialist Test Group at workshop 2nd July 2019, it was agreed that Carl Fratter would review the evidence on CHST14 by contacting their Thrombogenomics team to ask if they are able to provide any information on their experience, as they have included these genes in their panel. Gene rating to be confirmed when group has this information.
Intellectual disability v2.961 KCNJ11 Rebecca Foulger Publications for gene: KCNJ11 were set to
Intellectual disability v2.960 KCNJ11 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from BIALLELIC to BOTH monoallelic and biallelic, based on most papers in the literature reporting heterozygous activating variants in KCNJ11 with DD/ID as features: (e.g. PMIDs 25678012, 16670688, 27681997, 28943513).
Intellectual disability v2.960 KCNJ11 Rebecca Foulger Mode of inheritance for gene: KCNJ11 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v2.959 ATRX Rebecca Foulger Added comment: Comment on mode of inheritance: Changed Mode of inheritance from XLR to XLD: Alpha-thalassemia/mental retardation syndrome, 301040 is listed as XLD in OMIM (in addition to Mental retardation-hypotonic facies syndrome, X-linked, 309580 listed as XLR). Although PMID:17503331 report that nearly all female carriers of ATRX syndrome have highly skewed X-chromosome inactivation in favour of cells expressing the normal ATRX allele and are essentially phenotypically normal, PMID:16955409 report a female carrier where the chromosome carrying the mutant allele was active and she therefore showed a phenotype.
Intellectual disability v2.959 ATRX Rebecca Foulger Mode of inheritance for gene: ATRX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v2.958 ATRX Rebecca Foulger Publications for gene: ATRX were set to 25529582; 24896178; 26860117; 26997013; 10995512; 7697714; 12116232; 15565397; 8644709; 9244431; 9598720
Intellectual disability v2.957 ATRX Rebecca Foulger commented on gene: ATRX: PMID:16955409: Badens et al. 2006 report a 4 year old female with a heterozygous R246C variant in ATRX and a skewed pattern of X-inactivation where her maternally-inherited X chromosome that carried the de novo variant remained active. Clinical features included severed DD.
Intellectual disability v2.957 ATRX Rebecca Foulger commented on gene: ATRX
Intellectual disability v2.957 ATRX Rebecca Foulger Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, 301040Alpha-thalassemia myelodysplasia syndrome, somatic, 300448Mental retardation-hypotonic facies syndrome, X-linked, 309580; MENTAL RETARDATION SYNDROMIC X-LINKED WITH HYPOTONIC FACIES SYNDROME TYPE 1 (MRXSHF1) to Alpha-thalassemia/mental retardation syndrome, 301040; Mental retardation-hypotonic facies syndrome, X-linked, 309580
Intellectual disability v2.956 ATRX Rebecca Foulger Publications for gene: ATRX were set to
Early onset or syndromic epilepsy v1.171 ATRX Rebecca Foulger commented on gene: ATRX: PMID:16955409: Badens et al. 2006 report a 4 year old female with a heterozygous R246C variant in ATRX and a skewed pattern of X-inactivation where her maternally-inherited X chromosome that carried the de novo variant remained active. Clinical features included severed DD. Epilepsy/seizures were not reported amongst her phenotypes.
Fetal anomalies v0.306 NDP Rebecca Foulger Publications for gene: NDP were set to
Fetal anomalies v0.305 NDP Rhiannon Mellis reviewed gene: NDP: Rating: AMBER; Mode of pathogenicity: ; Publications: 30125416; Phenotypes: Norrie disease; Mode of inheritance:
Fetal anomalies v0.305 BRCA2 Lyn Chitty reviewed gene: BRCA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Fanconi anemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.50 PALB2 Helen Brittain Classified gene: PALB2 as Amber List (moderate evidence)
Severe microcephaly v1.50 PALB2 Helen Brittain Added comment: Comment on list classification: As per structural neurological working group webex on 11th July 2019
Severe microcephaly v1.50 PALB2 Helen Brittain Gene: palb2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v1.49 PALB2 Helen Brittain reviewed gene: PALB2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hydrocephalus v1.32 FMR1 Helen Brittain Classified gene: FMR1 as Red List (low evidence)
Hydrocephalus v1.32 FMR1 Helen Brittain Added comment: Comment on list classification: As per consensus agreement on structural neurological disorders webex on 11th July 2019
Hydrocephalus v1.32 FMR1 Helen Brittain Gene: fmr1 has been classified as Red List (Low Evidence).
Hydrocephalus v1.31 FMR1 Helen Brittain edited their review of gene: FMR1: Added comment: This gene was reviewed on the structural neurological disorders working group webex on 11th July. Although initially included on this panel in view of relative macrocephaly, this is not within the remit of the hydrocephalus panel for the GMS. In view of a lack of phenotypic relevance for SNVs and hydrocephalus, this gene was downgraded to red.; Changed rating: RED
Fetal anomalies v0.304 IARS Rebecca Foulger Phenotypes for gene: IARS were changed from Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, 617093
Fetal anomalies v0.303 IARS Rebecca Foulger Publications for gene: IARS were set to
Fetal anomalies v0.302 IARS Rebecca Foulger Classified gene: IARS as Green List (high evidence)
Fetal anomalies v0.302 IARS Rebecca Foulger Added comment: Comment on list classification: Promoted IARS from Amber to Green on advice from Genomics England clinical team. Although the DD-G2P Disease confidence rating is 'probable' for 'Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy', there are sufficient cases from the literature to support Green rating. As reviewed by Louise Daugherty on the 'Intellectual disability' panel: Kopajtich et al., 2016 PMID:27426735 reported 3 unrelated patients with a multisystem disorder characterized by intrauterine and postnatal growth retardation, including small head circumference (-3 to -5 SD), hypotonia and delayed psychomotor development with variable severity of intellectual disability.
Fetal anomalies v0.302 IARS Rebecca Foulger Gene: iars has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.22 IARS Rebecca Foulger Publications for gene: IARS were set to 27426735
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger commented on gene: IARS: Helen Brittain reviewed IARS on the 'Intellectual disability' panel' and notes: Early presentation with hypotonia and global delay.
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger commented on gene: IARS: DD-G2P Disease confidence rating of 'probable' for 'Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy', but sufficient cases from the literature to support Green rating. As reviewed by Louise Daugherty on the 'Intellectual disability' panel: Kopajtich et al., 2016 PMID:27426735 reported 3 unrelated patients with a multisystem disorder characterized by intrauterine and postnatal growth retardation, including small head circumference (-3 to -5 SD), hypotonia and delayed psychomotor development with variable severity of intellectual disability.
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger Classified gene: IARS as Green List (high evidence)
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger Gene: iars has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.20 IARS Rebecca Foulger gene: IARS was added
gene: IARS was added to Paediatric disorders - additional genes. Sources: Other
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, 617093
Added comment: Added to 'Paediatric disorders - additional genes' panel on recommendation of Genomics England clinical team.
Sources: Other
Paediatric disorders - additional genes v0.19 IER3IP1 Rebecca Foulger Classified gene: IER3IP1 as Green List (high evidence)
Paediatric disorders - additional genes v0.19 IER3IP1 Rebecca Foulger Gene: ier3ip1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.18 IER3IP1 Rebecca Foulger gene: IER3IP1 was added
gene: IER3IP1 was added to Paediatric disorders - additional genes. Sources: Other
Mode of inheritance for gene: IER3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IER3IP1 were set to 21835305; 22991235; 24138066
Phenotypes for gene: IER3IP1 were set to Microcephaly, epilepsy, and diabetes syndrome, 614231; MEDS
Added comment: Added to 'Paediatric disorders - additional genes' panel on recommendation of Genomics England clinical team, to allow demotion of gene rating on the 'Mitochondrial disorders' panel.
Sources: Other
Skeletal dysplasia v1.192 NIN Zornitza Stark reviewed gene: NIN: Rating: RED; Mode of pathogenicity: None; Publications: 22933543, 23665482; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v1.410 PITRM1 Catherine Snow Classified gene: PITRM1 as Green List (high evidence)
Mitochondrial disorders v1.410 PITRM1 Catherine Snow Added comment: Comment on list classification: PITRM1 identified by expert review by Konstantinos Varvagiannis on Intellectual Disability Panel https://panelapp.genomicsengland.co.uk/panels/285/.

Currently no OMIM or G2P phenotypes terms associated with the gene.

PMID: 29764912 reports on 2 consanguineous Palestinian families each with 2 affected boys. Both Palenstinian families are from Arab descent but are from different locale. PMID: 26697887 reports 2 siblings from a consanguineous Norwegian family homozygous for a missense variant (NM_014889.2:c.548G> or p.Arg183Gln). Although there is some functional work (PMID: 29383861) phenotypes are varied in severity.

There are sufficient unrelated families (>3) for PITRM1 to be classified as Green and PITRM1 is a mitochondrial matrix enzyme so therefore relevant to this panel.
Mitochondrial disorders v1.410 PITRM1 Catherine Snow Gene: pitrm1 has been classified as Green List (High Evidence).
Mitochondrial disorders v1.409 PITRM1 Catherine Snow Publications for gene: PITRM1 were set to 26697887; 29764912; 29383861
Mitochondrial disorders v1.409 PITRM1 Catherine Snow Publications for gene: PITRM1 were set to PMID: 26697887
Early onset or syndromic epilepsy v1.171 ATRX Rebecca Foulger Publications for gene: ATRX were set to 25606380: 11449489; 7697714; 11050622
Early onset or syndromic epilepsy v1.170 ATRX Rebecca Foulger Publications for gene: ATRX were set to Gibbons et al (1995) Cell 80: 837-845; Stevenson et al (2000) Am J Med Genet 94: 383-385
Early onset or syndromic epilepsy v1.169 ATRX Rebecca Foulger commented on gene: ATRX
Skeletal ciliopathies v0.10 LBR Eleanor Williams Phenotypes for gene: LBR were changed from Skeletal Ciliopathies to Skeletal Ciliopathies; Greenberg skeletal dysplasia, 215140
Skeletal ciliopathies v0.9 LBR Eleanor Williams Publications for gene: LBR were set to
Skeletal ciliopathies v0.8 LBR Eleanor Williams changed review comment from: Associated with Greenberg skeletal dysplasia 215140 as well as several other phenotypes in OMIM. Also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia. Associated with HYDROPS-ECTOPIC CALCIFICATION-MOTH-EATEN SKELETAL DYSPLASIA in Gene2Phenotype (confirmed).

From OMIM -
3 unrelated fetuses with Greenberg dysplasia, Clayton et al. (2010) identified homozygous or compound heterozygous mutations in the LBR gene. Functional assays suggests Greenberg dysplasia results from defects in the sterol reductase activity of LBR, not from the structural function of LBR as part of the nuclear membrane.

Waterham et al. (2003) found elevated levels of cholesta-8,14-dien-3-beta-ol in cultured skin fibroblasts of an 18-week-old fetus with HEM skeletal dysplasia, compatible with a deficiency of the cholesterol biosynthetic enzyme 3-beta-hydroxysterol delta(14)-reductase and identified a mutation in the LBR gene that resulted in a truncated protein.

PMID: 29068549 - Zhang et al 2018 - report a case of a neonate with a non-lethal form of asphyxiating thoracic dystrophy (ATD) and compound heterozygosity for missense mutations LBR . ; to: Associated with Greenberg skeletal dysplasia 215140 as well as several other phenotypes in OMIM. Also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia. Associated with HYDROPS-ECTOPIC CALCIFICATION-MOTH-EATEN SKELETAL DYSPLASIA in Gene2Phenotype (confirmed).

From OMIM -
PMID: 21327084 - Clayton et al. (2010) - 3 unrelated fetuses with Greenberg dysplasia. They identified homozygous or compound heterozygous mutations in the LBR gene. Functional assays suggests Greenberg dysplasia results from defects in the sterol reductase activity of LBR, not from the structural function of LBR as part of the nuclear membrane.

PMID: 12618959 Waterham et al. (2003) - found elevated levels of cholesta-8,14-dien-3-beta-ol in cultured skin fibroblasts of an 18-week-old fetus with HEM skeletal dysplasia, compatible with a deficiency of the cholesterol biosynthetic enzyme 3-beta-hydroxysterol delta(14)-reductase and identified a mutation in the LBR gene that resulted in a truncated protein.

PMID: 29068549 - Zhang et al 2018 - report a case of a neonate with a non-lethal form of asphyxiating thoracic dystrophy (ATD) and compound heterozygosity for missense mutations LBR .
Skeletal ciliopathies v0.8 Eleanor Williams Panel status changed from internal to public
Skeletal ciliopathies v0.7 LBR Eleanor Williams Classified gene: LBR as Green List (high evidence)
Skeletal ciliopathies v0.7 LBR Eleanor Williams Added comment: Comment on list classification: Updating from red to green. On the Skeletal ciliopathies panel (rather than the Multisystem ciliopathies panel), it was felt that it could be promoted to green even though the phenotype is not multisystem. It is highly likely to be relevant in childhood.
Skeletal ciliopathies v0.7 LBR Eleanor Williams Gene: lbr has been classified as Green List (High Evidence).
Intellectual disability v2.955 SLC9A6 Rebecca Foulger Publications for gene: SLC9A6 were set to
Early onset or syndromic epilepsy v1.169 SLC9A6 Rebecca Foulger Phenotypes for gene: SLC9A6 were changed from Mental retardation, X-linked syndromic, Christianson type to Mental retardation, X-linked syndromic, Christianson type, 300243
Early onset or syndromic epilepsy v1.168 SLC9A6 Rebecca Foulger Added comment: Comment on mode of inheritance: Comment on mode of inheritance: Changed the MOI from XLR to XLD based on Pescosolido et al., 2014 (PMID:25044251) who report some symptoms (mild to moderate ID) in heterozygous female carriers. Note that NHE6 is an alias for SLC9A6. Although Gene2Phenotype list a hemizygous inheritance for 'MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE' OMIM record an XLD inheritance for MIM:300243.
Early onset or syndromic epilepsy v1.168 SLC9A6 Rebecca Foulger Mode of inheritance for gene: SLC9A6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v2.954 SLC9A6 Rebecca Foulger changed review comment from: Comment on mode of inheritance: Changed the MOI from XLR to XLD based on Pescosolido et al., 2014 (PMID:25044251) who report mild to moderate ID in heterozygous female carriers.; to: Comment on mode of inheritance: Changed the MOI from XLR to XLD based on Pescosolido et al., 2014 (PMID:25044251) who report mild to moderate ID in heterozygous female carriers. Note that NHE6 is an alias for SLC9A6.
Intellectual disability v2.954 SLC9A6 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed the MOI from XLR to XLD based on Pescosolido et al., 2014 (PMID:25044251) who report mild to moderate ID in heterozygous female carriers.
Intellectual disability v2.954 SLC9A6 Rebecca Foulger Mode of inheritance for gene: SLC9A6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v2.953 CTBP1 Chris Buxton reviewed gene: CTBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27094857, 31041561; Phenotypes: intellectual disability, ataxia, hypotonia, tooth enamel defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v1.145 CEP290 Tom Cullup reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17345604; Phenotypes: LEBER CONGENITAL AMAUROSIS 10, LCA10; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paediatric disorders - additional genes v0.17 Rebecca Foulger Panel types changed to GMS Rare Disease; Component Of Super Panel
Paediatric disorders v3.528 Rebecca Foulger Changed child panels to: Intellectual disability; Skeletal dysplasia; Rare multisystem ciliopathy disorders; DDG2P; Inborn errors of metabolism; Familial non syndromic congenital heart disease; Limb disorders; Paediatric disorders - additional genes
Unexplained kidney failure in young people v1.73 Eleanor Williams Panel name changed from End-stage renal disease - childhood onset to Unexplained kidney failure in young people
List of related panels changed from Unexplained kidney failure in young people; Familial IgA nephropathy and IgA vasculitis; End-stage renal disease - childhood onset to Familial IgA nephropathy and IgA vasculitis; End-stage renal disease - childhood onset
Unexplained kidney failure in young people v1.72 Eleanor Williams List of related panels changed from Unexplained kidney failure in young people; Familial IgA nephropathy and IgA vasculitis to Unexplained kidney failure in young people; Familial IgA nephropathy and IgA vasculitis; End-stage renal disease - childhood onset
Skeletal dysplasia v1.192 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - 2 cases. Case 1 - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Case 2 - They also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.; to: PMID: 22019273 - Bredrup et al. (2011) - 2 cases. Case 1 - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Case 2 - They also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies (such as right-convex scoliosis and congenital hip dysplasia), strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.
Skeletal dysplasia v1.192 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.; to: PMID: 22019273 - Bredrup et al. (2011) - 2 cases. Case 1 - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Case 2 - They also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.
Skeletal dysplasia v1.192 NIN Eleanor Williams changed review comment from: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM. ; to: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S). The p.N1709S is a novel variant that is not present in Single Nucleotide Polymorphism database, 1000 Genomes pilot data, or the NHLBI exome variant server. The p.Q1222R was present only in the 1000 Genomes pilot data with an overall minor allele frequency of 0.001 (0.005 in the Americas subcohort). In patient derived primary dermal fibroblasts, the compound heterozygous NIN defects did not disrupt Ninein expression or localization or obviously affect mitotic functions. But zebrafish nin morphilino knockdowns include phenotypes such as reduced growth and altered patterning of the skull, consistent with general phenotypic characteristics of MPD.

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM.
Skeletal dysplasia v1.192 IFT43 Eleanor Williams changed review comment from: Associated with ?Cranioectodermal dysplasia 3 (#614099) and Short-rib thoracic dysplasia 18 with polydactyly (#617866) in OMIM and with CRANIOECTODERMAL DYSPLASIA TYPE 3 (confirmed) in Gene2Phenotype.

PMID: 21378380- Arts et al. 2011 - 1 case . 2 siblings from a consanguineous family of Moroccan descent with cranioectodermal dysplasia (Sensenbrenner syndrome). The reported phenotype includes Rhizomelic shortening of limbs, narrow thorax, toe syndactyly, brachydactyly, and polydactyly (one sibling). Following genome-wide homozygosity mapping two candidate genes were analyzed and a homozygous missense mutation in the translation initiation codon of the IFT43 gene was identified. Fibroblasts from one of the affected siblings (II:2) show a typical IFT-A defect (ie, accumulation of IFT-B complex proteins in the ciliary tip.

PMID: 28400947 - Duran et al. 2017- 2 cases - in 3 affected individuals from 2 unrelated families with short-rib thoracic dysplasia with polydactyly thye identified homozygosity for missense mutations in the IFT143 gene, M1K and W179R.

PMID: 26892345 - Stokman et al 2016 - 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. They de novo 4.5-Mb microdeletion which contains 65 protein-coding genes, including the ciliary gene IFT43. Immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport.; to: Associated with ?Cranioectodermal dysplasia 3 (#614099) and Short-rib thoracic dysplasia 18 with polydactyly (#617866) in OMIM and with CRANIOECTODERMAL DYSPLASIA TYPE 3 (confirmed) in Gene2Phenotype.

PMID: 21378380- Arts et al. 2011 - 1 case . 2 siblings from a consanguineous family of Moroccan descent with cranioectodermal dysplasia (Sensenbrenner syndrome). The reported phenotype includes Rhizomelic shortening of limbs, narrow thorax, toe syndactyly, brachydactyly, and polydactyly (one sibling). Following genome-wide homozygosity mapping two candidate genes were analyzed and a homozygous missense mutation in the translation initiation codon of the IFT43 gene was identified. Fibroblasts from one of the affected siblings (II:2) show a typical IFT-A defect (ie, accumulation of IFT-B complex proteins in the ciliary tip.

PMID: 28400947 - Duran et al. 2017- 2 cases - in 3 affected individuals from 2 unrelated families with short-rib thoracic dysplasia with polydactyly they identified homozygosity for missense mutations in the IFT143 gene, M1K and W179R.

PMID: 26892345 - Stokman et al 2016 - 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. They de novo 4.5-Mb microdeletion which contains 65 protein-coding genes, including the ciliary gene IFT43. Immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport.
Skeletal dysplasia v1.192 GZF1 Eleanor Williams Classified gene: GZF1 as Green List (high evidence)
Skeletal dysplasia v1.192 GZF1 Eleanor Williams Gene: gzf1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Deleted their comment
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Classified gene: GZF1 as Amber List (moderate evidence)
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber as a result of expert review. Only 2 cases although there is some functional evidence supporting the role of this protein in the disease.
Skeletal dysplasia v1.191 GZF1 Eleanor Williams Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.190 GPX4 Eleanor Williams Classified gene: GPX4 as Amber List (moderate evidence)
Skeletal dysplasia v1.190 GPX4 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber. 3 variants but only 2 cases.
Skeletal dysplasia v1.190 GPX4 Eleanor Williams Gene: gpx4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.189 B9D1 Eleanor Williams Classified gene: B9D1 as Amber List (moderate evidence)
Skeletal dysplasia v1.189 B9D1 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Amber, as the association with a skeletal phenotype is not clear.
Skeletal dysplasia v1.189 B9D1 Eleanor Williams Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.188 ADAMTS17 Eleanor Williams Classified gene: ADAMTS17 as Green List (high evidence)
Skeletal dysplasia v1.188 ADAMTS17 Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported with patients with short stature.
Skeletal dysplasia v1.188 ADAMTS17 Eleanor Williams Gene: adamts17 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.187 ADAMTS17 Eleanor Williams Publications for gene: ADAMTS17 were set to
Skeletal dysplasia v1.186 ADAMTS17 Eleanor Williams Mode of inheritance for gene: ADAMTS17 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.185 RAB33B Eleanor Williams Publications for gene: RAB33B were set to
Skeletal dysplasia v1.184 RAB33B Eleanor Williams Classified gene: RAB33B as Green List (high evidence)
Skeletal dysplasia v1.184 RAB33B Eleanor Williams Added comment: Comment on list classification: 5 cases reported.
Skeletal dysplasia v1.184 RAB33B Eleanor Williams Gene: rab33b has been classified as Green List (High Evidence).
Skeletal dysplasia v1.183 PAM16 Eleanor Williams Classified gene: PAM16 as Amber List (moderate evidence)
Skeletal dysplasia v1.183 PAM16 Eleanor Williams Added comment: Comment on list classification: 3 cases, but two are likely to share the same founder mutation. Rating amber until further cases are reported.
Skeletal dysplasia v1.183 PAM16 Eleanor Williams Gene: pam16 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.182 PAM16 Eleanor Williams changed review comment from: Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.; to: Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with distantly related Argentinian parents of central European descent, with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.
Skeletal dysplasia v1.182 PAM16 Eleanor Williams changed review comment from: PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.; to: Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.
Skeletal dysplasia v1.182 PAM16 Eleanor Williams changed review comment from: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PAM16; Initial rating suggestion: green; to: This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PAM16; Initial rating suggestion: green
Skeletal dysplasia v1.182 MMP9 Eleanor Williams changed review comment from: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Only 2 cases reported, 3rd had variant in MMP13 not MMP9.; to: Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Only 2 cases reported, 3rd had variant in MMP13 not MMP9.

Mouse model - PMID: 9590175 - Vu et al. 1998 - report that homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification.
Skeletal dysplasia v1.182 MMP9 Eleanor Williams Publications for gene: MMP9 were set to 28342220; 24781753; 19615667
Skeletal dysplasia v1.181 MMP9 Eleanor Williams Classified gene: MMP9 as Amber List (moderate evidence)
Skeletal dysplasia v1.181 MMP9 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber as two cases have been reported with variants in this gene.
Skeletal dysplasia v1.181 MMP9 Eleanor Williams Gene: mmp9 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.180 MATN3 Eleanor Williams Publications for gene: MATN3 were set to
Skeletal dysplasia v1.179 MATN3 Eleanor Williams Classified gene: MATN3 as Green List (high evidence)
Skeletal dysplasia v1.179 MATN3 Eleanor Williams Added comment: Comment on list classification: More than 3 cases of variants in this gene in patients with a relevant phenotype.
Skeletal dysplasia v1.179 MATN3 Eleanor Williams Gene: matn3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.178 MATN3 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving mode of inheritance as monoallelelic, as only one case reported of biallelic variants causing Spondyloepimetaphyseal Dysplasia so far.
Skeletal dysplasia v1.178 MATN3 Eleanor Williams Mode of inheritance for gene: MATN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.177 MATN3 Eleanor Williams changed review comment from: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.; to: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).
PMID: PMID: 30080953 - Pettersson et al 2018 - in a 17‐year‐old girl born to healthy, nonconsanguineous parents of Caucasian origin who was diagnosed with multiple epiphyseal dysplasia they identified a heterozygous intragenic duplication within MATN3, affecting exons 2–5 by custom array‐CGH.

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.
Skeletal dysplasia v1.177 MATN3 Eleanor Williams changed review comment from: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia including:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.; to: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.
Skeletal dysplasia v1.177 MATN3 Eleanor Williams commented on gene: MATN3: Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.

Epiphyseal dysplasia including:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).

Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.

Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.
Skeletal dysplasia v1.177 FZD2 Eleanor Williams Classified gene: FZD2 as Green List (high evidence)
Skeletal dysplasia v1.177 FZD2 Eleanor Williams Added comment: Comment on list classification: More than 3 cases with variants in FZD2 in patients with a relevant phenotype.
Skeletal dysplasia v1.177 FZD2 Eleanor Williams Gene: fzd2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.176 FZD2 Eleanor Williams changed review comment from: Associated with Omodysplasia 2 (164745) in OMIM.

PMID: 25759469 - Saal et al 2015 - 1 family. proband with omodysplasia, her unaffected parents and her affected daughter. Identified a de novo mutation (c.1644G>A, p.Trp548*) in FZD2 in the proband and her daughter that was not found in unaffected family members. Show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2.

PMID: 29230162 - Türkmen et al 2017 - 1 patient. A heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits.

PMID: 29383830 - invalid pubmed id

PMID: 29383834 - Nagasaki et al 2018 - 1 patient. 16-year-old boy with OMOD2 or Robinow syndrome-like phenotype. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2.

PMID: 30455931 - Warren et al 2018 - 2 patients. Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. The mutations identified have been recently reported, suggesting the possibility of recurrent mutations. The phenotypes of these patients overlap with what has been previously reported, though intellectual disability as seen in our patient is not typical.

Total of 4 cases; to: Associated with Omodysplasia 2 (164745) in OMIM.

PMID: 25759469 - Saal et al 2015 - 1 family. proband with omodysplasia, her unaffected parents and her affected daughter. Identified a de novo mutation (c.1644G>A, p.Trp548*) in FZD2 in the proband and her daughter that was not found in unaffected family members. Show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2.

PMID: 29230162 - Türkmen et al 2017 - 1 patient. A heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits.

PMID: 29383830 - invalid pubmed id

PMID: 29383834 - Nagasaki et al 2018 - 1 patient. 16-year-old boy with OMOD2 or Robinow syndrome-like phenotype. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2.

PMID: 30455931 - Warren et al 2018 - 2 patients. Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. Patient 1 has a p.Trp548* alteration previously reported. Patient 2 has missense alteration p.Gly434Val also previously reported. The phenotypes of these patients overlap with what has been previously reported, though patient 2 also presented with intellectual disability which is not typical.

Total of 4 cases
Skeletal dysplasia v1.176 FN1 Eleanor Williams Added comment: Comment on mode of pathogenicity: Only missense or inframe deletions reported to date.
Skeletal dysplasia v1.176 FN1 Eleanor Williams Mode of pathogenicity for gene: FN1 was changed from to Other
Skeletal dysplasia v1.175 FN1 Eleanor Williams Classified gene: FN1 as Green List (high evidence)
Skeletal dysplasia v1.175 FN1 Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported of plausible disease causing mutations found in the FN1 gene in patients with a relevant phenotype.
Skeletal dysplasia v1.175 FN1 Eleanor Williams Gene: fn1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.174 FN1 Eleanor Williams Publications for gene: FN1 were set to 29100092
Skeletal dysplasia v1.173 FN1 Eleanor Williams Mode of inheritance for gene: FN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.172 FN1 Eleanor Williams commented on gene: FN1: This gene is associated with Spondylometaphyseal dysplasia, corner fracture type (#184255) in OMIM.

PMID: 29100092 - Lee et al 2017 - 7 cases. Variants in FN1 found in patients from 7 families with Spondylometaphyseal dysplasias with corner fractures. 2 cases were familial, the rest were de novo mutations. In the two familial cases inheritance was autosomal dominant. All FN1 variants discovered in this study are absent from the ExAC Browser and affect highly conserved residues. 6 of the variants were missense, and one was an inframe deletion.

PMID: 30599297 - Costantini et al 2019 - 5 cases. Using WGS/WES or targeted Sanger sequencing they identified 5 heterozygous missense variants in FN1 in patients with spondylometaphyseal dysplasia with "corner fractures" (SMD-CF). In two families the variant was inherited from an affected parent. None of the patients had impaired renal function.
Skeletal dysplasia v1.172 ADAMTS17 Eleanor Williams commented on gene: ADAMTS17: Associated with Weill-Marchesani 4 syndrome, recessive #613195 in OMIM. This condition is characterized by short stature and brachydactyly as well as eye-associated clinical features.

PMID: 19836009 - Morales et al. 2009 - 3 cases from Saudi Arabia, 2 familial and 1 sporadic. 7 affected individuals. All had short stature and ocular manifestations but not brachydactyly so are described as WMS-like. 3 different homozygous variants were detected (1 bp insertion, a splice-site mutation, and a nonsense mutation).

PMID: 22486325 - Khan et al. 2012 - 1 case. A sister and brother with WMS from a consanguineous Saudi family were found to have a 1-bp deletion that segregated with disease. The probands presented with high myopia and had spherophakia. Although both had short stature, neither had short hands, short feet, joint stiffness, or non-ocular congenital abnormalities

PMID: 24940034 - Shah et al. 2014 - 1 case. In an Indian family WES analysis identified a homozygous novel splice-site mutation c.873+1G>T in ADAMTS1 in a 21 year old proband. RT-PCR analysis in the patient showed that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the ADAMTS17 protein. The proband presented with decreased vision. She had short stature, brachydactyly, but no joint stiffness.

PMID: 31019231 - Yi et al 2019 - 1 case. In a consanguineous Chinese family, a nonsense mutation c.1051 A > T in ADAMTS17 was identified. (Abstract only accessed).

More than 3 cases. Short stature reported but brachydactyly only in 1 case.
Skeletal dysplasia v1.172 ADAMTS10 Eleanor Williams Phenotypes for gene: ADAMTS10 were changed from Weill-Marchesani syndrome type 1 to Weill-Marchesani syndrome 1, recessive, 277600
Skeletal dysplasia v1.171 ADAMTS10 Eleanor Williams Publications for gene: ADAMTS10 were set to
Skeletal dysplasia v1.170 ADAMTS10 Eleanor Williams Mode of inheritance for gene: ADAMTS10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.169 ADAMTS10 Eleanor Williams Classified gene: ADAMTS10 as Green List (high evidence)
Skeletal dysplasia v1.169 ADAMTS10 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as there are more than 3 cases with variants in ADAMS10 in patients with Weill-Marchesani syndrome. Plus a mouse model with a WMS associated truncating mutation has a skeletal phenotype.
Skeletal dysplasia v1.169 ADAMTS10 Eleanor Williams Gene: adamts10 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.168 ADAMTS10 Eleanor Williams commented on gene: ADAMTS10: Associated with Weill-Marchesani syndrome 1, recessive (#277600) in OMIM.

PMID: 15368195 - Dagoneau et al. 2004 - 3 cases. following homozygosity-mapping strategy in two consanguineous families from Lebanon and Saudi Arabia with Weill-Marchesani syndrome they selected ADAMTS10 for further sequencing. They found three distinct mutations of the ADAMTS10 gene in these two families and in one sporadic WMS case (one nonsense mutation (R237X) and two splice-site mutations). The variants segregated with the disease in the familial cases. All probands fulfilled the criteria for WMS with short stature, brachydactyly, limitation of joint movement, microspherophakia, dislocated lenses, severe myopia, and glaucoma.

PMID: 19836009 - Morales et al. 2009 - 2 cases. Two families which met the diagnostic criteria for WMS were each found to have a different homozygous missense mutation in ADAMTS10 (c.1553 G > A (p.G518D) and c.2098 G > T (p.G700C)).

PMID: 30060141 - Mularczyk et al 2018 - A mouse model containing a truncation mutation on ADAMS10 seen in WMS patients was created. Homozygous WMS mice are smaller and have shorter long bones with perturbation to the zones of the developing growth plate and changes in cell proliferation.
Early onset or syndromic epilepsy v1.167 DEGS1 Konstantinos Varvagiannis gene: DEGS1 was added
gene: DEGS1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEGS1 were set to 30620337; 30620338; 31186544
Phenotypes for gene: DEGS1 were set to Leukodystrophy hypomyelinating 18, 618404
Penetrance for gene: DEGS1 were set to Complete
Review for gene: DEGS1 was set to GREEN
Added comment: Several individuals with biallelic pathogenic DEGS1 variants have been reported to date, in the following studies :
[1] Pant et al. 2019 (PMID: 30620337) : 19 patients from 13 unrelated families
[2] Karsai et al. 2019 (PMID: 30620338) : 1 individual
[3] Dolgin et al. 2019 (PMID: 31186544) : 4 individuals belonging to a large consanguineous kindred

As summarized in the first article and OMIM, affected individuals may have very poor psychomotor development, dystonia, spasticity, seizures with hypomyelinating leukodystrophy upon brain imaging and/or progressive atrophy of corpus callosum, thalami and cerebellum. Although a severe form overall was reported for many individuals in the first study, variable severity (eg. mild to severe ID) was reported among individuals belonging to the same kindred in the report by Dolgin et al.

DEGS1 encodes Δ4-dehydroceramide desaturase which catalyzes conversion of dihydroceramide (DhCer) to ceramide (Cer) in the de novo ceramide biosynthetic pathway. Ceramide is the central unit of all sphingolipids, which are components of cellular membranes and play key roles in several processes incl. cell differentiation, neuronal signaling and myelin sheath formation.

Sphingolipid balance is important for the CNS as demonstrated in the case of lysosomal disorders (eg. Gaucher, Niemann Pick, Farber) one enzymatic step away from DEGS1.

Variants of all types (missense, stopgain, frameshift) have been reported with the majority/almost all located in the fatty acid desaturase (FAD) domain.

Extensive studies have been carried out and demonstrated:
- impaired DEGS1 activity in patients' fibroblasts and muscle suggested by increased DhCer/Cer ratio and compatible broader biochemical effects (higher levels of dihydrosphingosine, dihydrosphingomyelins, etc. and lower levels of sphingosine, monohexosylceramides, etc).
- increased ROS production in patient fibroblasts (similar to a Drosophila model of excess DhCer),
- high expression of the gene in child and adult CNS tissues from control individuals (evaluated by RT-qPCR in Ref. 1). A previous study has suggested that DEGS1 expression is upregulated during the 4-9th week of human embryogenesis (PMID cited: 20430792) which may suggest an important role for neural system development.
- decreased expression for some variants either evaluated at the mRNA (RT-qPCR) / protein level (by Western Blot)
- In zebrafish loss of Degs1 resulted in increased DhCer/Cer ratio, locomotor disability and impaired myelination similar to the patients' phenotype. Fingolimod, a sphingosine analog inhibiting Cer synthase (one step prior to DEGS1 in the de novo ceramide biosynthesis pathway, and converting sphingosine to ceramide in the salvage pathway) reduced the DhCer/Cer imbalance, ameliorated the locomotor phenotype and increased the number of myelinating oligodendrocytes in zebrafish, while it reduced the ROS levels in patient fibroblasts.

Previous animal models:
Apart from the zebrafish model (Pant et al.), higher DhCer/Cer ratios have been shown in homozygous Degs1 -/- mice similar to what is also observed in D. melanogaster. As summarized in MGI (and the previous studies as well) "mice homozygous for a knock-out allele exhibit premature death, decreased to absent ceramide levels, decreased body weight, scaly skin, sparse hair, tremors, hematological and blood chemistry abnormalities, decreased bone mineral content and density and decreased liver function." (PMIDs cited: 17339025, 28507162).
----
The respective OMIM entry is Leukodystrophy, hypomyelinating, 18 (#618404). DEGS1 is not associated with any phenotype in G2P.
----
As a result, DEGS1 can be considered for inclusion in the ID and epilepsy panels probably as green (relevant phenotype, sufficient number of individuals, supportive expression and biochemical studies, animal models, etc).
Sources: Literature
Intellectual disability v2.953 DEGS1 Konstantinos Varvagiannis gene: DEGS1 was added
gene: DEGS1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEGS1 were set to 30620337; 30620338; 31186544
Phenotypes for gene: DEGS1 were set to Leukodystrophy hypomyelinating 18, MIM 618404)
Penetrance for gene: DEGS1 were set to Complete
Review for gene: DEGS1 was set to GREEN
Added comment: Several individuals with biallelic pathogenic DEGS1 variants have been reported to date, in the following studies :
[1] Pant et al. 2019 (PMID: 30620337) : 19 patients from 13 unrelated families
[2] Karsai et al. 2019 (PMID: 30620338) : 1 individual
[3] Dolgin et al. 2019 (PMID: 31186544) : 4 individuals belonging to a large consanguineous kindred

As summarized in the first article and OMIM, affected individuals may have very poor psychomotor development, dystonia, spasticity, seizures with hypomyelinating leukodystrophy upon brain imaging and/or progressive atrophy of corpus callosum, thalami and cerebellum. Although a severe form overall was reported for many individuals in the first study, variable severity (eg. mild to severe ID) was reported among individuals belonging to the same kindred in the report by Dolgin et al.

DEGS1 encodes Δ4-dehydroceramide desaturase which catalyzes conversion of dihydroceramide (DhCer) to ceramide (Cer) in the de novo ceramide biosynthetic pathway. Ceramide is the central unit of all sphingolipids, which are components of cellular membranes and play key roles in several processes incl. cell differentiation, neuronal signaling and myelin sheath formation.

Sphingolipid balance is important for the CNS as demonstrated in the case of lysosomal disorders (eg. Gaucher, Niemann Pick, Farber) one enzymatic step away from DEGS1.

Variants of all types (missense, stopgain, frameshift) have been reported with the majority/almost all located in the fatty acid desaturase (FAD) domain.

Extensive studies have been carried out and demonstrated:
- impaired DEGS1 activity in patients' fibroblasts and muscle suggested by increased DhCer/Cer ratio and compatible broader biochemical effects (higher levels of dihydrosphingosine, dihydrosphingomyelins, etc. and lower levels of sphingosine, monohexosylceramides, etc).
- increased ROS production in patient fibroblasts (similar to a Drosophila model of excess DhCer),
- high expression of the gene in child and adult CNS tissues from control individuals (evaluated by RT-qPCR in Ref. 1). A previous study has suggested that DEGS1 expression is upregulated during the 4-9th week of human embryogenesis (PMID cited: 20430792) which may suggest an important role for neural system development.
- decreased expression for some variants either evaluated at the mRNA (RT-qPCR) / protein level (by Western Blot)
- In zebrafish loss of Degs1 resulted in increased DhCer/Cer ratio, locomotor disability and impaired myelination similar to the patients' phenotype. Fingolimod, a sphingosine analog inhibiting Cer synthase (one step prior to DEGS1 in the de novo ceramide biosynthesis pathway, and converting sphingosine to ceramide in the salvage pathway) reduced the DhCer/Cer imbalance, ameliorated the locomotor phenotype and increased the number of myelinating oligodendrocytes in zebrafish, while it reduced the ROS levels in patient fibroblasts.

Previous animal models:
Apart from the zebrafish model (Pant et al.), higher DhCer/Cer ratios have been shown in homozygous Degs1 -/- mice similar to what is also observed in D. melanogaster. As summarized in MGI (and the previous studies as well) "mice homozygous for a knock-out allele exhibit premature death, decreased to absent ceramide levels, decreased body weight, scaly skin, sparse hair, tremors, hematological and blood chemistry abnormalities, decreased bone mineral content and density and decreased liver function." (PMIDs cited: 17339025, 28507162).
----
The respective OMIM entry is Leukodystrophy, hypomyelinating, 18 (#618404). DEGS1 is not associated with any phenotype in G2P.
----
As a result, DEGS1 can be considered for inclusion in the ID and epilepsy panels probably as green (relevant phenotype, sufficient number of individuals, supportive expression and biochemical studies, animal models, etc).
Sources: Literature
Fetal anomalies v0.301 GBE1 Rebecca Foulger Publications for gene: GBE1 were set to
Skeletal dysplasia v1.168 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .; to: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient (previously described in Vries et al, 2010) with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .

3 cases in total.
Skeletal dysplasia v1.168 WDR19 Eleanor Williams changed review comment from: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .; to: PMID: 22019273 - Bredrup et al. (2011) - sister and brother with cranioectodermal dysplasia (Sensenbrenner syndrome) identified compound heterozygosity for variants in the WDR19 gene that cosegregated with disease (L710S, and R1103X, 608151.0002). Also found a a Dutch patient with Jeune syndrome (asphyxiating thoracic dysplasia) and homozygosity for a missense mutation in WDR19 (L7P).

PMID: 24504730 - Fehrenbach et al 2014 - 8 year old girl with hypotonia, facial dysmorphism and retardation which were noted shortly after birth. Other features included short stature, mild skeletal anomalies, strabism, deafness, subdural hygroma, hepatosplenomegaly and end-stage renal failure. Identified novel homozygous WDR19 mutation c.1483G > C (p.Gly495Arg) .
Skeletal dysplasia v1.168 TMEM67 Eleanor Williams changed review comment from: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3
PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.; to: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case:

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3 - 3 out of 22 cases show polydactyly:

PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.
Skeletal dysplasia v1.168 TMEM67 Eleanor Williams commented on gene: TMEM67: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361).

RHYNS syndrome - 1 case

PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents.

PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done.

Meckel syndrome 3
PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families.

PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.
Bardet Biedl syndrome v0.22 WDPCP Ivone Leong Publications for gene: WDPCP were set to 20671153
Bardet Biedl syndrome v0.21 WDPCP Ivone Leong Classified gene: WDPCP as Amber List (moderate evidence)
Bardet Biedl syndrome v0.21 WDPCP Ivone Leong Added comment: Comment on list classification: Demoted from green to amber. There are several unrelated cases of oral-facial-digital syndromes caused by variants in WDPCP; however, there is only 1 case of BBS (PMID: 28289185,25427950 and 27158779). Therefore, this gene has been demoted to amber.
Bardet Biedl syndrome v0.21 WDPCP Ivone Leong Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Optic neuropathy v1.116 SSBP1 Ivone Leong Publications for gene: SSBP1 were set to PMID: 31298765
Limb disorders v1.8 RBPJ Eleanor Williams Publications for gene: RBPJ were set to 22883147; 28160419
Limb disorders v1.7 RBPJ Eleanor Williams commented on gene: RBPJ
Skeletal dysplasia v1.168 RBPJ Eleanor Williams Publications for gene: RBPJ were set to 28160419; 22883147
Optic neuropathy v1.115 SSBP1 Anna de Burca Classified gene: SSBP1 as Green List (high evidence)
Optic neuropathy v1.115 SSBP1 Anna de Burca Gene: ssbp1 has been classified as Green List (High Evidence).
Optic neuropathy v1.114 SSBP1 Anna de Burca reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31298765; Phenotypes: Autosomal dominant optic atrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation; to: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. All 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 22883147 - Hassed et al. [2012] identified mutations in RBPJ through exome sequencing in two independent kindreds with autosomal dominant AOS.

PMID: 28160419 - Hassad et al 2017 - don't think they report any new families.; to: PMID: 22883147 - Hassed et al. 2012 - identified mutations in RBPJ through exome sequencing in two independent kindreds with autosomal dominant AOS.

PMID: 28160419 - Hassad et al 2017 - don't think they report any new families.
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation; to: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 RBPJ Eleanor Williams changed review comment from: PMID: 29924900 - Meester et al 2018 - analyzed cohort comprised 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation; to: PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Skeletal dysplasia v1.167 RBPJ Eleanor Williams commented on gene: RBPJ: PMID: 29924900 - Meester et al 2018 - analyzed cohort comprised 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ) They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. In all 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocation
Optic neuropathy v1.114 SSBP1 Tom Cullup changed review comment from: Sources: Expert list; to: Sources: Expert list

Variants identified to date are missense and putative mode of action is dominant-negative, therefore there is potential for exception to loss-of-function rule, but insufficient data to clearly demonstrate at the moment. There are lower than expected LoF variants in gnomAD, so cannot rule out pathogenic LoF variants.
Optic neuropathy v1.114 SSBP1 Tom Cullup gene: SSBP1 was added
gene: SSBP1 was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: SSBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SSBP1 were set to PMID: 31298765
Phenotypes for gene: SSBP1 were set to Autosomal dominant optic atrophy with variable retinal degeneration
Penetrance for gene: SSBP1 were set to Complete
Review for gene: SSBP1 was set to GREEN
Added comment: Sources: Expert list
Bleeding and platelet disorders v0.68 ABCG8 Mandy nesbitt changed review comment from: Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.; to: Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.
Bleeding and platelet disorders v0.68 COL3A1 Mandy nesbitt reviewed gene: COL3A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 130050 Ehlers-Danlos syndrome, vascular type, 618343 Polymicrogyria with or without vascular-type EDS; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and platelet disorders v0.68 CHST14 Mandy nesbitt reviewed gene: CHST14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 601776 Ehlers-Danlos syndrome, musculocontractural type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.167 NIN Eleanor Williams changed review comment from: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype.; to: PMID: 22933543 - Dauber et al. (2012) -2 sisters with severe short stature, microcephaly, and developmental delay (Seckel syndrome-7) were identified to have compound heterozygosity for missense mutations in the NIN gene (Q1222R; N1709S)

PMID: 23665482 -Grosch et al (2013) - in a consanguineous family with a phenotype resembling Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) they identified homozygous missense mutations in the two nearby genes NIN and POLE2 which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. They present evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The NIN variant is classified as a VUS in OMIM.
Skeletal dysplasia v1.167 IFT81 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

Summary - 2 cases, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype; to: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

PMID: 30080953 - Pettersson et al 2018 - a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD). He had narrow thorax, short arms, brachydactyly and short stature. Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples.

Summary - 2 cases with SNVs and strong skeletal phenotype, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype. 4th case with tandem duplication of 2 exons.
Skeletal dysplasia v1.167 IFT81 Eleanor Williams commented on gene: IFT81: Associated with Short-rib thoracic dysplasia 19 with or without polydactyly (#617895) in OMIM

PMID: 27666822 - Duran et al 2016 - 2 cases. Family 1 - male infant (R98-443) with features consistent with Asphyxiating thoracic dystrophy (ATD). The radiographic abnormalities included midface hypoplasia, dolichocephaly, a prominent occiput , short ribs, handlebar clavicles and short, curved appendicular bones, with the upper limbs particularly abnormally shaped. There was no polydactyly on either the hands or feet. They identified compound heterozygosity for two variants: p.Leu29Phe and p.Arg512*. Family 2 - fetus (R13-147A) suspected to have SRPS by prenatal ultrasonography. Postnatal radiographs showed dolichocephaly, a prominent occiput, midface hypoplasia, a very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses and marked hypoplasia of the radii, ulnae, tibiae and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. They identified compound heterozygosity for variants in IFT81: p.Leu262 and p.Leu435del). Cultured chondrocytes from one patient showed decreased levels of transcript. Mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components

PMID: 26275418 - Perrault et al 2015 - identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. The variant has been classified as a VUS in OMIM as its contribution to nephronophthisis-related ciliopathy has not be confirmed.

PMID: 28460050 - Dharmat et al 2017 - Compound heterozygous mutations in IFT81 were identified in a nonsyndromic Cone rod dystrophy proband.

Summary - 2 cases, one with some functional data. 3rd case with polydactyly the only skeletal component of the phenotype
Skeletal dysplasia v1.167 IFT52 Eleanor Williams Publications for gene: IFT52 were set to 26880018; 27466190
Skeletal dysplasia v1.166 IFT52 Eleanor Williams changed review comment from: Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.

PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.

PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.

PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.

PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.; to: Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.

PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.

PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.

PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.

PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.

Summary - 3 cases plus a 4th with a milder skeletal phenotype.
Skeletal dysplasia v1.166 IFT52 Eleanor Williams commented on gene: IFT52: Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.

PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.

PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.

PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.

PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.
Skeletal dysplasia v1.166 IFT43 Eleanor Williams commented on gene: IFT43: Associated with ?Cranioectodermal dysplasia 3 (#614099) and Short-rib thoracic dysplasia 18 with polydactyly (#617866) in OMIM and with CRANIOECTODERMAL DYSPLASIA TYPE 3 (confirmed) in Gene2Phenotype.

PMID: 21378380- Arts et al. 2011 - 1 case . 2 siblings from a consanguineous family of Moroccan descent with cranioectodermal dysplasia (Sensenbrenner syndrome). The reported phenotype includes Rhizomelic shortening of limbs, narrow thorax, toe syndactyly, brachydactyly, and polydactyly (one sibling). Following genome-wide homozygosity mapping two candidate genes were analyzed and a homozygous missense mutation in the translation initiation codon of the IFT43 gene was identified. Fibroblasts from one of the affected siblings (II:2) show a typical IFT-A defect (ie, accumulation of IFT-B complex proteins in the ciliary tip.

PMID: 28400947 - Duran et al. 2017- 2 cases - in 3 affected individuals from 2 unrelated families with short-rib thoracic dysplasia with polydactyly thye identified homozygosity for missense mutations in the IFT143 gene, M1K and W179R.

PMID: 26892345 - Stokman et al 2016 - 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. They de novo 4.5-Mb microdeletion which contains 65 protein-coding genes, including the ciliary gene IFT43. Immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport.
Skeletal dysplasia v1.166 ICK Eleanor Williams commented on gene: ICK: Mouse model data

PMID: 24853502 - Moon et al 2014 - Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes.

PMID: 24797473 - Chaya et al 2014 - ICK−/− mice died around birth probably because of respiratory failure. ICK−/− mice exhibited preaxial polydactyly in both fore and hind limbs. All four limbs were severely shortened in the ICK−/− mice at E18.5

PMID: 28380258 - Tong et al 2017 - created an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Their report focusses on the respiratory phenotype, but they report that mice displayed essential ECO pathological features such as polydactyly and shortened limbs.
Skeletal dysplasia v1.166 ICK Eleanor Williams changed review comment from: PMID: 19185282 - Lahiry et al. (2009) - in 6 affected infants with Endocrine-Cerebroosteodysplasia of Old Order Amish pedigree a homozygous mutation was identified in the ICK gene. The phenotype was severe, involved several organ systems, and resulted in fetal or neonatal death.

PMID: 27069622 Oud et al. (2016) - a Turkish fetus with Endocrine-Cerebroosteodysplasia was found to be homozygous for a missense mutation in the ICK gene that segregated fully with disease in the family and was not found in Turkish controls or public variant databases

PMID: 27466187 Paige Taylor et al (2016) - identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one short rib polydactyly syndromes family.; to: PMID: 19185282 - Lahiry et al. (2009) - in 6 affected infants with Endocrine-Cerebroosteodysplasia of Old Order Amish pedigree a homozygous mutation (R272Q) was identified in the ICK gene. The phenotype was severe, involved several organ systems, and resulted in fetal or neonatal death.

PMID: 27069622 Oud et al. (2016) - a Turkish fetus with Endocrine-Cerebroosteodysplasia was found to be homozygous for a missense mutation (G120C) in the ICK gene that segregated fully with disease in the family and was not found in Turkish controls or public variant databases

PMID: 27466187 Paige Taylor et al (2016) - identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one short rib polydactyly syndromes family.
Skeletal dysplasia v1.166 GZF1 Eleanor Williams commented on gene: GZF1: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and with LARSEN SYNDROME (probable) in Gene2Phenotype. Generalized joint laxity is listed as a phenotype for Larsen syndrome in Gene2Phenotype.

PMID: 28475863 - Patel et al 2017 - 2 cases. Family 1 - a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia. The index patient also had severe kyphoscoliosis. Both the index patient and her brother had short stature. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity) A second homozygous truncating GZF1 variant was identified (c.1054dup (p.Thr352Asnfs∗50). Neither variant was present in 2,379 Saudi exomes or the Exome Aggregation Consortium (ExAC) Browser. In functional studies they found using immunofluorescence, strong localization of GZF1 in the developing mouse eye and, to a lesser extent, in the mesenchyme of the developing mouse limb buds. Using 3 patient-derived lymphoblastoid cell lines they found 1,095 genes to be dysregulated in affected individuals.
Tubulointerstitial kidney disease v0.14 MUC1 Eleanor Williams Added comment: Comment on publications: Added PMID: 23946964 Bleyer and Kmoch, last updated 2016. Gene reviews entry on Autosomal Dominant Tubulointerstitial Kidney Disease, MUC1-Related
Tubulointerstitial kidney disease v0.14 MUC1 Eleanor Williams Publications for gene: MUC1 were set to 23396133; 29967284; 29156055; 29520014
Tubulointerstitial kidney disease v0.13 MUC1 Eleanor Williams Added comment: Comment on publications: Added PMID: 29520014 Wenzel et al 2018 which describes long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay.
Tubulointerstitial kidney disease v0.13 MUC1 Eleanor Williams Publications for gene: MUC1 were set to 23396133; 29967284; 29156055
Skeletal dysplasia v1.166 B9D1 Eleanor Williams commented on gene: B9D1: Associated with ?Meckel syndrome 9 (#614209) and Joubert syndrome 27 (#617120) in OMIM.
Gene2Phenotype reports a probable association with MECKEL SYNDROME 9.

PMID: 24886560 - Romani et al 2014 - report mutations in B9D1 in two patients, a 9-year-old boy (COR363) and a 7-year-old girl (COR346), both presenting with pure JS. The mutations (cG467A; p.R156Q homo, and cA95G; p.Y32C, c.520-522delGTG; p.V175del) were inherited from heterozygous healthy parents, were not reported in public databases, and affected highly conserved residues. Missense mutations were predicted as pathogenic by prediction web tools. Neither patient showed polydactyly or orofacial features although patient COR363's facial dysmorphisms included a triangular face, retrognatism, accentuated philtrum and big ears, and patient COR346's dysmorphic facial features included frontal bossing, macrostomia, thick lips and low-set ears.

PMID: 21493627 - Hopp et al 2011 - In family M456 with Meckel syndrome (MKS), a splice-donor site change in B9D1 was detected in a fetus (c.505+2T>C). Sanger sequencing revealed likely hemizygosity of this variant, with a de novo deletion of the B9D1 locus in the fetus. The deletion spans 1.713 Mb at chromosome 17p11.2, including the complete B9D1 locus. Additionally, 18 other genes were deleted. The authors also identified a novel change in a second MKS gene, CEP290. Sanger sequencing showed that the heterozygous variant, p.R2210C, was inherited from the mother.
Polydactyly, that is typical in MKS, was not noted but the fetus had bilateral club feet and shortened limbs.
Fetal anomalies v0.300 MYO7A Rebecca Foulger changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is not fetally-relevant. Additional notes from clinical review: Disease confidence in DD-G2P is 'both DD and IF'. Nothing structural that would present in a fetus. Action taken: Demoted KIT gene rating from Amber to Red.; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is not fetally-relevant. Additional notes from clinical review: Disease confidence in DD-G2P is 'both DD and IF'. Nothing structural that would present in a fetus. Action taken: Demoted MYO7A gene rating from Amber to Red.
Early onset or syndromic epilepsy v1.167 PIGB Konstantinos Varvagiannis gene: PIGB was added
gene: PIGB was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGB were set to 31256876
Phenotypes for gene: PIGB were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Hearing abnormality; Abnormality of vision; Elevated alkaline phosphatase; Abnormality of the head; Abnormality of the hand; Abnormality of the foot
Penetrance for gene: PIGB were set to Complete
Review for gene: PIGB was set to GREEN
Added comment: Murakami et al. (2019 - PMID: 31256876) provide detailed information on 14 individuals from 10 families (4 of which consanguineous) with biallelic pathogenic PIGB variants.

Overlapping features included DD/ID (13/13), epilepsy (14/14), deafness (7/14), ophthalmological or brain anomalies, hand and feet anomalies as well as presence of dysmorphic features. ID was common, in those individuals with appropriate age. Some had a previous diagnosis of DOORS syndrome (deafness/onychodystrophy/osteodystrophy,retardation, seizures) and few showed 2-oxoglutatic aciduria which can also be seen in DOORS s.

PIGB encodes phosphatidylinositol glycan anchor biosynthesis class B protein.

Overall the phenotype was similar to other inherited glycosylphosphatidylinositol (GPI) deficiencies (IGDs). As happens to be the case in some other GPI deficiencies alkaline phosphatase was also elevated in those tested (8/9).

8 missense, 1 stopgain as well as an intronic SNV are reported. All variants were either absent or ultra-rare and with no homozygotes in gnomAD.

Affected individuals from 4 families, harbored an intronic SNV in the homozygous state. For this variant - with MAF of 0.0001592 or 6.51x10-5 in ExAC and gnomAD - activation of an aberrant splice acceptor site was shown [NM_004855.4:c.847-10A>G or p.Gln282_Trp283insArgCysGln].

Flow cytometric analysis of blood cells or fibroblasts showed decreased levels for various GPI-AP (GPI-anchored protein) markers in affected individuals. These levels were rescued upon transduction with a PIGB-encoding-Lx304 lentiviral vector of fibroblasts from one affected individual, suggesting that the PIGB defect was responsible.

The effect of the variants was evaluated using PIGB-deficient CHO cells, transfected with wt or mutant PIGB cDNAs. FACS analysis and immunoblotting demonstrated that variants were able to restore only slightly/partially - if at all - the surface presence of GPI-APs in the case of variants while the levels of mutant protein were reduced.

PIGB is not associated with any phenotype in OMIM/G2P. This gene is not commonly included in gene panels for ID offered by diagnostic laboratories.

As a result, this gene can be considered for inclusion in the ID and epilepsy panels probably as green (or amber).
Sources: Literature
Intellectual disability v2.953 PIGB Konstantinos Varvagiannis gene: PIGB was added
gene: PIGB was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGB were set to 31256876
Phenotypes for gene: PIGB were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Hearing abnormality; Abnormality of vision; Elevated alkaline phosphatase; Abnormality of the head; Abnormality of the hand; Abnormality of the foot
Penetrance for gene: PIGB were set to Complete
Review for gene: PIGB was set to GREEN
Added comment: Murakami et al. (2019 - PMID: 31256876) provide detailed information on 14 individuals from 10 families (4 of which consanguineous) with biallelic pathogenic PIGB variants.

Overlapping features included DD/ID (13/13), epilepsy (14/14), deafness (7/14), ophthalmological or brain anomalies, hand and feet anomalies as well as presence of dysmorphic features. ID was common, in those individuals with appropriate age. Some had a previous diagnosis of DOORS syndrome (deafness/onychodystrophy/osteodystrophy,retardation, seizures) and few showed 2-oxoglutatic aciduria which can also be seen in DOORS s.

PIGB encodes phosphatidylinositol glycan anchor biosynthesis class B protein.

Overall the phenotype was similar to other inherited glycosylphosphatidylinositol (GPI) deficiencies (IGDs). As happens to be the case in some other GPI deficiencies alkaline phosphatase was also elevated in those tested (8/9).

8 missense, 1 stopgain as well as an intronic SNV are reported. All variants were either absent or ultra-rare and with no homozygotes in gnomAD.

Affected individuals from 4 families, harbored an intronic SNV in the homozygous state. For this variant - with MAF of 0.0001592 or 6.51x10-5 in ExAC and gnomAD - activation of an aberrant splice acceptor site was shown [NM_004855.4:c.847-10A>G or p.Gln282_Trp283insArgCysGln].

Flow cytometric analysis of blood cells or fibroblasts showed decreased levels for various GPI-AP (GPI-anchored protein) markers in affected individuals. These levels were rescued upon transduction with a PIGB-encoding-Lx304 lentiviral vector of fibroblasts from one affected individual, suggesting that the PIGB defect was responsible.

The effect of the variants was evaluated using PIGB-deficient CHO cells, transfected with wt or mutant PIGB cDNAs. FACS analysis and immunoblotting demonstrated that variants were able to restore only slightly/partially - if at all - the surface presence of GPI-APs in the case of variants while the levels of mutant protein were reduced.

PIGB is not associated with any phenotype in OMIM/G2P. This gene is not commonly included in gene panels for ID offered by diagnostic laboratories.

As a result, this gene can be considered for inclusion in the ID and epilepsy panels probably as green (or amber).
Sources: Literature
Early onset or syndromic epilepsy v1.167 TRAK1 Sarah Leigh Phenotypes for gene: TRAK1 were changed from Fatal encephalopathy to Epileptic encephalopathy, early infantile, 68 618201
Mitochondrial DNA maintenance disorder v0.10 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to
Possible mitochondrial disorder - nuclear genes v0.206 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to
Early onset or syndromic epilepsy v1.166 SLC9A6 Rebecca Foulger Publications for gene: SLC9A6 were set to Gilfillan et al (2008) Am J Hum Genet 82: 1003_1010
Congenital hypothyroidism v1.29 Ivone Leong List of related panels changed from Congenital hypothyroidism or thyroid agenesis to Congenital hypothyroidism or thyroid agenesis; R145
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Congenital hyperinsulinism v1.51 SLC16A1 Ivone Leong Phenotypes for gene: SLC16A1 were changed from Hyperinsulinism, Dominant; Erythrocyte lactate transporter defect, 245340 to Hyperinsulinism, Dominant; Erythrocyte lactate transporter defect, 245340; Autosomal dominant exercise-induced hyperinsulinism
Congenital hyperinsulinism v1.50 KMT2D Ivone Leong Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1 to Kabuki syndrome 1, 147920; Autosomal dominant neonatal hypoglycaemia as part of Kabuki syndrome
Congenital hyperinsulinism v1.49 KDM6A Ivone Leong Phenotypes for gene: KDM6A were changed from Kabuki syndrome 2 to Kabuki syndrome 2, 300867; X-linked dominant neonatal hypoglycaemia as part of Kabuki syndrome
Congenital hyperinsulinism v1.48 INSR Ivone Leong Phenotypes for gene: INSR were changed from Leprechaunism, 246200; hyperinsulinemic hypoglycaemia to Leprechaunism, 246200; hyperinsulinemic hypoglycaemia; Autosomal dominant postprandial hypoglycaemia
Congenital hyperinsulinism v1.47 HNF4A Ivone Leong Phenotypes for gene: HNF4A were changed from Hyperinsulinism, Dominant to Hyperinsulinism, Dominant; Autosomal dominant Hyperinsulinism; MODY, type I, 125850
Congenital hyperinsulinism v1.46 HNF1A Ivone Leong Phenotypes for gene: HNF1A were changed from to Autosomal dominant Hyperinsulinism; MODY, type III, 600496
Congenital hyperinsulinism v1.45 HADH Ivone Leong Phenotypes for gene: HADH were changed from Congenital hyperinsulinemic hypoglycemia (HH); Hyperinsulinism, Dominant/Recessive; 3-hydroxyacyl-CoA dehydrogenase deficiency, 231530 to Congenital hyperinsulinemic hypoglycemia (HH); Hyperinsulinism, Dominant/Recessive; 3-hydroxyacyl-CoA dehydrogenase deficiency, 231530; Protein sensitive hyperinsulinism
Congenital hyperinsulinism v1.44 GPC3 Ivone Leong Phenotypes for gene: GPC3 were changed from neonatal hypoglycaemia; distinctive craniofacies, congenital heart defects, genitourinary defects, GI anomalies, skeletal anomalies; supernumerary nipples to neonatal hypoglycaemia; distinctive craniofacies, congenital heart defects, genitourinary defects, GI anomalies, skeletal anomalies; supernumerary nipples; X-linked recessive hypoglycaemia as part of Simpson-Golabi-Behmel syndrome (312870)
Congenital hyperinsulinism v1.43 FOXA2 Ivone Leong Phenotypes for gene: FOXA2 were changed from Hyperinsulinism; hypopituitarism to Hyperinsulinism; hypopituitarism; Dominant Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities
Congenital hyperinsulinism v1.42 AKT2 Ivone Leong Phenotypes for gene: AKT2 were changed from hypoinsulinemic hypoketotic hypoglycemia to hypoinsulinemic hypoketotic hypoglycemia, 240900; Autosomal dominant fasting hypoglycaemia and asymmetrical overgrowth
Congenital hyperinsulinism v1.41 Ivone Leong List of related panels changed from Hyperinsulinism to Hyperinsulinism; R144
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Neonatal diabetes v1.45 WFS1 Ivone Leong Phenotypes for gene: WFS1 were changed from Syndromic neonatal diabetes to Syndromic neonatal diabetes; Wolfram syndrome, 222300
Neonatal diabetes v1.44 STAT3 Ivone Leong Phenotypes for gene: STAT3 were changed from Neonatal diabetes and additional multi-organ autoimmunity; permanent neonatal diabetes to Neonatal diabetes and additional multi-organ autoimmunity; permanent neonatal diabetes; Neonatal diabetes and early-onset multi-organ autoimmune disease
Neonatal diabetes v1.43 SLC2A2 Ivone Leong Phenotypes for gene: SLC2A2 were changed from Fanconi-Bickel syndrome, 227810; neonatal diabetes mellitus; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes (PDNM) to Fanconi-Bickel syndrome, 227810; neonatal diabetes mellitus; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes (PDNM); Fanconi Bickel Syndrome; neonatal diabetes; short stature; hepatomegaly, RTA and hypophosphatemic rickets
Neonatal diabetes v1.42 SLC19A2 Ivone Leong Phenotypes for gene: SLC19A2 were changed from Thiamine-responsive megaloblastic anemia syndrome, 249270; neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia (TRMA); permanent neonatal diabetes (PNDM) to Thiamine-responsive megaloblastic anemia syndrome, 249270; neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia (TRMA); permanent neonatal diabetes (PNDM); Thiamine responsive megaloblastic anaemia; neonatal diabetes
Neonatal diabetes v1.41 RFX6 Ivone Leong Phenotypes for gene: RFX6 were changed from Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes) to Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes); Syndromic Neonatal diabetes; pancreatic hypoplasia, gallbladder aplasia and intestinal atresia; Mitchell-Riley syndrome
Neonatal diabetes v1.40 NKX2-2 Ivone Leong Phenotypes for gene: NKX2-2 were changed from Neonatal diabetes to Neonatal diabetes; Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment
Neonatal diabetes v1.39 NEUROG3 Ivone Leong Phenotypes for gene: NEUROG3 were changed from Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes to Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes; Syndromic neonatal diabetes with malabsorptive diarrhea (neurointestinal dysplasia, intrahepatic bilary tract, abnormalities of thyroid gland and CNS)
Neonatal diabetes v1.38 NEUROD1 Ivone Leong Phenotypes for gene: NEUROD1 were changed from Permanent neonatal diabetes and cerebellar agenesis to Permanent neonatal diabetes and cerebellar agenesis; Neonatal diabetes and cerebellar agenesis, rocker bottom feet, poorly developed renal cortex and medulla, sacral agenesis, high imperforate anus; Maturity-onset diabetes of the young 6, 606394
Neonatal diabetes v1.37 MNX1 Ivone Leong Phenotypes for gene: MNX1 were changed from Neonatal Diabetes; Permanent neonatal diabetes mellitus (PNDM) to Neonatal Diabetes; Permanent neonatal diabetes mellitus (PNDM); Recessive Neonatal diabetes; IUGR; w w/o eatures of Currarrino syndrome and sacral agenesis; Currarino syndrome, 176450
Neonatal diabetes v1.36 LRBA Ivone Leong Phenotypes for gene: LRBA were changed from Immunodysregulation and type 1 diabetes; Immunodeficiency, common variable, 8, with autoimmunity, 614700; IPEX-like syndrome to Immunodysregulation and type 1 diabetes; Immunodeficiency, common variable, 8, with autoimmunity, 614700; IPEX-like syndrome; Neonatal diabetes and additional autoimmunity
Neonatal diabetes v1.35 KCNJ11 Ivone Leong Phenotypes for gene: KCNJ11 were changed from Hyperinsulinemic hypoglycemia, familial, 2, 601820; Diabetes, permanent neonatal, 606176; Diabetes mellitus, permanent neonatal, with neurologic features, 606176; {Diabetes mellitus, type 2, susceptibility to}, 125853; Diabetes mellitus, transient neonatal, 3, 610582; Transient Neonatal Diabetes, Dominant; Diabetes Mellitus, PermanentNeonatal; Diabetes Mellitus, Transient Neonatal, 3; Transient Neonatal diabetes mellitus (Dominant) to Hyperinsulinemic hypoglycemia, familial, 2, 601820; Diabetes, permanent neonatal, 606176; Diabetes mellitus, permanent neonatal, with neurologic features, 606176; {Diabetes mellitus, type 2, susceptibility to}, 125853; Diabetes mellitus, transient neonatal, 3, 610582; Transient Neonatal Diabetes, Dominant; Diabetes Mellitus, PermanentNeonatal; Diabetes Mellitus, Transient Neonatal, 3; Transient Neonatal diabetes mellitus (Dominant); Isolated permanent neonatal diabetes; isolated transient neonatal diabetes, neonatal diabetes and developmental delay
Neonatal diabetes v1.34 INSR Ivone Leong Phenotypes for gene: INSR were changed from neonatal diabetes to neonatal diabetes; Donohue syndrome, 246200
Neonatal diabetes v1.33 IL2RA Ivone Leong Phenotypes for gene: IL2RA were changed from neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942 to neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942; Neoantal diabetes, congenital hypothyrodism (multiple autoimmune) Recessive
Neonatal diabetes v1.32 HNF1B Ivone Leong Phenotypes for gene: HNF1B were changed from Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus; Diabetes mellitus, noninsulin-dependent, 125853 to Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus; Diabetes mellitus, noninsulin-dependent, 125853; Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW
Neonatal diabetes v1.31 GCK Ivone Leong Phenotypes for gene: GCK were changed from MODY, type II, 125851; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Diabetes mellitus, gestational, 125851; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Recessive; Permanent neonatal diabetes to MODY, type II, 125851; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Diabetes mellitus, gestational, 125851; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Recessive; Permanent neonatal diabetes; Fasting hyperglycaemia, permanent neonatal diabetes
Neonatal diabetes v1.30 GATA6 Ivone Leong Phenotypes for gene: GATA6 were changed from Pancreatic agenesis and congenital heart defects, 600001; neonatal diabetes mellitus to Pancreatic agenesis and congenital heart defects, 600001; neonatal diabetes mellitus; Pancreatic agenesis and congenital heart defects
Neonatal diabetes v1.29 EIF2S3 Ivone Leong Phenotypes for gene: EIF2S3 were changed from diabetes; intellectual disability; microcephaly; epilepsy; hypogonadism; hypogenitalism; central obesity to diabetes; intellectual disability; microcephaly; epilepsy; hypogonadism; hypogenitalism; central obesity; MEHMO syndrome (X-linked NDM and microcephaly),300148
Neonatal diabetes v1.28 BSCL2 Ivone Leong Phenotypes for gene: BSCL2 were changed from Congenital generalised lipodystrophy, severe insulin resistance and diabetes to Congenital generalised lipodystrophy, severe insulin resistance and diabetes; Neonatal diabetes and generalised lipodystrophy; Lipodystrophy, congenital generalized, type 2, 269700
Possible mitochondrial disorder - nuclear genes v0.205 NDUFAF7 Sarah Leigh Publications for gene: NDUFAF7 were set to
Mitochondrial disorder with complex I deficiency v0.67 NDUFAF7 Sarah Leigh Publications for gene: NDUFAF7 were set to
Early onset or syndromic epilepsy v1.165 KCNJ11 Rebecca Foulger Publications for gene: KCNJ11 were set to 25678012; 16670688; 16609879; 27681997; 17065345
Neonatal diabetes v1.27 ABCC8 Ivone Leong Phenotypes for gene: ABCC8 were changed from Hyperinsulinemic hypoglycemia, familial, 1, 256450; Hypoglycemia of infancy, leucine-sensitive, 240800; Diabetes mellitus, transient neonatal 2, 610374; Diabetes mellitus, noninsulin-dependent, 125853; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Dominant; Permanent neonatal diabetes mellitus; transient neonatal diabetes (Dominant) to Hyperinsulinemic hypoglycemia, familial, 1, 256450; Hypoglycemia of infancy, leucine-sensitive, 240800; Diabetes mellitus, transient neonatal 2, 610374; Diabetes mellitus, noninsulin-dependent, 125853; Diabetes mellitus, permanent neonatal, 606176; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Dominant; Permanent neonatal diabetes mellitus; transient neonatal diabetes (Dominant); Isolated permanent neonatal diabetes; isolated transient neonatal diabetes, neonatal diabetes and developmental delay
Neonatal diabetes v1.26 Ivone Leong List of related panels changed from Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months to Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; R143
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Monogenic diabetes v1.38 ZBTB20 Ivone Leong Phenotypes for gene: ZBTB20 were changed from Primrose syndrome to Primrose syndrome, 259050; Primrose syndrome (tall stature, macrocephaly, intellectual disability, disturbed behaviour, unusual facial features, diabetes, deafness, progressive muscle wasting and ectopic calcifications)
Monogenic diabetes v1.37 TRMT10A Ivone Leong Phenotypes for gene: TRMT10A were changed from failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability to failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability; Autosomal recessive juvenile-onset diabetes with microcephaly, epilepsy and intellectual disability; Microcephaly, short stature, and impaired glucose metabolism 1, 616033
Monogenic diabetes v1.36 SLC29A3 Ivone Leong Phenotypes for gene: SLC29A3 were changed from Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome to Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome; H syndrome (hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and hyperglycaemia) and PHID syndrome (pigmented hypertrichosis with insulin dependent diabetes); Histiocytosis-lymphadenopathy plus syndrome,602782
Monogenic diabetes v1.35 RFX6 Ivone Leong Phenotypes for gene: RFX6 were changed from Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome to Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710; recessive syndromic diabetes and autosomal dominant MODY
Monogenic diabetes v1.34 PPP1R15B Ivone Leong Phenotypes for gene: PPP1R15B were changed from to Autosomal recessive juvenile-onset diabetes with microcephaly, epilepsy and intellectual disability,616817
Monogenic diabetes v1.33 POLD1 Ivone Leong Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, 615381; multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males; Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, 615381; multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males; Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome; multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males; Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, 615381
Monogenic diabetes v1.32 PLIN1 Ivone Leong Phenotypes for gene: PLIN1 were changed from partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes; Lipodystrophy, familial partial, type 4, 613877 to partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes; Lipodystrophy, familial partial, type 4, 613877; Severe insulin resistance, partial lipodystrophy and diabetes
Monogenic diabetes v1.31 PIK3R1 Ivone Leong Phenotypes for gene: PIK3R1 were changed from Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome; SHORT syndrome to Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome, 269880; SHORT syndrome
Monogenic diabetes v1.30 PDX1 Ivone Leong Phenotypes for gene: PDX1 were changed from Pancreatic agenesis 1; MODY4; Maturity-Onset Diabetes Of The Young; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 4; Permanent neonatal diabetes; Maturity-onset diabetes of the young (MODY); MODY type IV to Pancreatic agenesis 1; MODY4; Maturity-Onset Diabetes Of The Young; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 4; Permanent neonatal diabetes; Maturity-onset diabetes of the young (MODY); MODY type IV; Recessive neonatal diabetes, pancreatic agenesis and dominant MODY, 606392
Monogenic diabetes v1.29 PCBD1 Ivone Leong Phenotypes for gene: PCBD1 were changed from Hyperphenylalaninemia, BH4-deficient, D to Hyperphenylalaninemia, BH4-deficient, D, 264070; Recessive neonatal hyperphenylalaninemia and later onset diabetes (puberty)
Monogenic diabetes v1.28 PAX6 Ivone Leong Phenotypes for gene: PAX6 were changed from to Aniridia 106210; diabetes
Monogenic diabetes v1.27 MT-TL1 Ivone Leong Phenotypes for gene: MT-TL1 were changed from MIDD; DIABETES AND DEAFNESS, MATERNALLY INHERITED; Diabetes-Deafness Syndrome, Maternally Transmitted; MELAS syndrome to MIDD; DIABETES AND DEAFNESS, MATERNALLY INHERITED; Diabetes-Deafness Syndrome, Maternally Transmitted; MELAS syndrome; Maternally inherited diabetes
Monogenic diabetes v1.26 LMNA Ivone Leong Phenotypes for gene: LMNA were changed from FPLD2; LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2; Lipodystrophy, familial partial, 2, 151660; Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules to FPLD2; LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 2; Lipodystrophy, familial partial, 2, 151660; Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules; Severe insulin resistance, partial lipodystrophy and diabetes
Monogenic diabetes v1.25 HNF4A Ivone Leong Phenotypes for gene: HNF4A were changed from {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity-Onset Diabetes Of The Young; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 1; MODY1; Maturity-onset diabetes of the young (MODY); MODY, type I, 125850; OMIM 616026; Maturity Onset Diabetes of the Young to {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity-Onset Diabetes Of The Young, Type 1; MODY1, 125850; Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young 616026
Monogenic diabetes v1.24 HNF4A Ivone Leong Phenotypes for gene: HNF4A were changed from {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity-Onset Diabetes Of The Young; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 1; MODY1; Maturity-onset diabetes of the young (MODY); MODY, type I, 125850; OMIM 616026; #616026; Maturity Onset Diabetes of the Young to {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity-Onset Diabetes Of The Young; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 1; MODY1; Maturity-onset diabetes of the young (MODY); MODY, type I, 125850; OMIM 616026; Maturity Onset Diabetes of the Young
Monogenic diabetes v1.23 GCK Ivone Leong Phenotypes for gene: GCK were changed from Transient Neonatal Diabetes, Recessive; MODY2; Diabetes mellitus, permanent neonatal, 606176; Maturity-Onset Diabetes Of The Young; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Permanent neonatal diabetes; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 2; Permanent Neonatal Diabetes Mellitus (recessive); Maturity-onset diabetes of the young (MODY); Permanent Neonatal Diabetes Mellitus; Maturity Onset Diabetes of the Young (Dominant); Diabetes mellitus, gestational, 125851; MODY, type II, 125851; Maturity Onset Diabetes of the Young to Transient Neonatal Diabetes, Recessive; MODY2; Diabetes mellitus, permanent neonatal, 606176; Maturity-Onset Diabetes Of The Young; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Permanent neonatal diabetes; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 2; Permanent Neonatal Diabetes Mellitus (recessive); Maturity-onset diabetes of the young (MODY); Permanent Neonatal Diabetes Mellitus; Maturity Onset Diabetes of the Young (Dominant); Diabetes mellitus, gestational, 125851; MODY, type II, 125851; Maturity Onset Diabetes of the Young; Neonatal diabetes; Fasting hyperglycaemia
Monogenic diabetes v1.22 GATA6 Ivone Leong Publications for gene: GATA6 were set to 22806356; 25706805; 23635550; 24433315; 24310933; 23639568; 22158542; 26210631; 22962692; 27098067; 25708516; Lango Allen et al 2011 Nat Genet 44, 20-22 De Franco et al 2013 Diabetes 62, 993-997; 25356219
Monogenic diabetes v1.21 GATA6 Ivone Leong Phenotypes for gene: GATA6 were changed from Pancreatic agenesis and congenital heart defects; PANCREATIC AGENESIS AND CONGENITAL HEART DEFECTS to Pancreatic agenesis and congenital heart defects; PANCREATIC AGENESIS AND CONGENITAL HEART DEFECTS; Metabolic syndrome (coronary artery disease, hypertension, central obesity and diabetes)
Monogenic diabetes v1.20 GATA4 Ivone Leong Phenotypes for gene: GATA4 were changed from Neonatal diabetes, Pancreatic agenesis and/or congenital heart defects to Neonatal diabetes; Pancreatic agenesis and/or congenital heart defects; Metabolic syndrome (coronary artery disease, hypertension, central obesity and diabetes)
Monogenic diabetes v1.19 DNAJC3 Ivone Leong Phenotypes for gene: DNAJC3 were changed from ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192 to ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192; Autosomal recessive juvenile-onset diabetes with central and peripheral neurodegeneration
Monogenic diabetes v1.18 CEL Ivone Leong Phenotypes for gene: CEL were changed from Maturity-onset diabetes of the young, type VIII, 609812 to Maturity-onset diabetes of the young, type VIII, 609812; Diabetes and pancreatic exocrine dysfunction
Monogenic diabetes v1.17 APPL1 Ivone Leong Phenotypes for gene: APPL1 were changed from {Maturity-onset diabetes of the young, type 14}, 616511 to {Maturity-onset diabetes of the young, type 14}, 616511; Diabetes
Monogenic diabetes v1.16 DCAF17 Ivone Leong Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome, 241080 to Woodhouse-Sakati syndrome, 241080; Woodhouse-Sakati syndrome (hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness)
Monogenic diabetes v1.15 AKT2 Ivone Leong Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853 to Diabetes mellitus, type II, 125853; Severe insulin resistance, partial lipodystrophy and diabetes
Monogenic diabetes v1.14 DYRK1B Ivone Leong Phenotypes for gene: DYRK1B were changed from to Abdominal obesity-metabolic syndrome 3, 615812; Metabolic syndrome (coronary artery disease, hypertension, central obesity and diabetes)
Monogenic diabetes v1.13 DNAJC3 Ivone Leong Phenotypes for gene: DNAJC3 were changed from to ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192
Monogenic diabetes v1.12 DCAF17 Ivone Leong Phenotypes for gene: DCAF17 were changed from to Woodhouse-Sakati syndrome, 241080
Intellectual disability v2.953 DEAF1 Rebecca Foulger Phenotypes for gene: DEAF1 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 24 to MENTAL RETARDATION, AUTOSOMAL DOMINANT 24; ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Monogenic diabetes v1.11 APPL1 Ivone Leong Phenotypes for gene: APPL1 were changed from to {Maturity-onset diabetes of the young, type 14}, 616511
Intellectual disability v2.952 DEAF1 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed the MOI from 'MONOALLELIC' to 'BOTH monoallelic and biallelic' based on PMID:30923367. Nabais et al., 2019 investigated AD and AR DEAF1 variants in a cohort of 23 patients. With the exception of microcephaly, most phenotypes (including ID, DD and seizures) were reported in patients with biallelic and pathogenic de novo DEAF1 variants.
Intellectual disability v2.952 DEAF1 Rebecca Foulger Mode of inheritance for gene: DEAF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic diabetes v1.10 AKT2 Ivone Leong Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II to Diabetes mellitus, type II, 125853
Monogenic diabetes v1.9 Ivone Leong List of related panels changed from to R141
Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Early onset or syndromic epilepsy v1.164 DEAF1 Rebecca Foulger Publications for gene: DEAF1 were set to 26048982; 28940898; 26834045; 30109124
Early onset or syndromic epilepsy v1.163 DEAF1 Rebecca Foulger Added comment: Comment on mode of inheritance: PMID:30923367 supports the 'BOTH monoallelic and biallelic' MOI:. Nabais et al., 2019 investigated AD and AR DEAF1 variants in a cohort of 23 patients. With the exception of microcephaly, most phenotypes (including ID, DD and seizures) were reported in patients with biallelic and pathogenic de novo DEAF1 variants.
Early onset or syndromic epilepsy v1.163 DEAF1 Rebecca Foulger Mode of inheritance for gene: DEAF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pituitary hormone deficiency v1.2 Ivone Leong List of related panels changed from to R159
Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v1.2 Ivone Leong List of related panels changed from to R151
Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Hypogonadotropic hypogonadism (GMS) v0.28 Ivone Leong List of related panels changed from to R148
Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Hypophosphataemia or rickets v1.3 Ivone Leong List of related panels changed from to R154
Familial tumoral calcinosis v0.12 Ivone Leong List of related panels changed from to R162
Panel types changed to GMS Rare Disease; GMS signed-off
Primary pigmented nodular adrenocortical disease v0.10 Ivone Leong List of related panels changed from to R160
Panel types changed to GMS Rare Disease; GMS signed-off
Familial hypoparathyroidism v1.11 Ivone Leong List of related panels changed from Familial or syndromic hypoparathyroidism to Familial or syndromic hypoparathyroidism; R153
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Lipodystrophy - childhood onset v1.8 Ivone Leong List of related panels changed from to R158
Early onset or syndromic epilepsy v1.162 CNKSR2 Rebecca Foulger Mode of inheritance for gene: CNKSR2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v1.161 CNKSR2 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated mode of inheritance from XLR to XLD based on PMID:28098945, so that affected females are detected. Damiano et al., 2017 report the first female with a CNKSR2 variant and childhood epilepsy- the sister had a less severe phenotype than her two brothers, which could be subject to X-inactivation (not directly measured). The mother, who also carries the point mutation, had only febrile seizures.
Early onset or syndromic epilepsy v1.161 CNKSR2 Rebecca Foulger Mode of inheritance for gene: CNKSR2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v1.160 CNKSR2 Rebecca Foulger Publications for gene: CNKSR2 were set to 28098945; 25223753; 22511892
Inherited phaeochromocytoma and paraganglioma excluding NF1 v0.6 Ivone Leong List of related panels changed from to R223
Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Endocrine neoplasia v0.5 Ivone Leong List of related panels changed from to R217
Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Congenital adrenal hypoplasia v1.11 Ivone Leong List of related panels changed from to R150
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Early onset or syndromic epilepsy v1.159 CACNA1D Rebecca Foulger Mode of pathogenicity for gene: CACNA1D was changed from None to Other
Early onset or syndromic epilepsy v1.158 CACNA1D Rebecca Foulger Publications for gene: CACNA1D were set to 28472301; 23913001; 30698561
Early onset or syndromic epilepsy v1.157 CACNA1D Rebecca Foulger Added comment: Comment on mode of inheritance: Primary aldosteronism, seizures, and neurologic abnormalities (MIM: 615474) has AD inheritance. Seizures are not generally reported for the biallelic disorder Sinoatrial node dysfunction and deafness (MIM:614896). However, PMID:30054272 report an Arabic individual from consanguineous parents with moderate hearing impairment, ID, DD and epilepsy and a homozygous missense variant in CACNA1D (Gln567His). Seizures began age 4 months. The individual also had a homozygous OTOG variant, but this was present in a heterozygous state in the gnomAD browser. Both parents were heterozygous for the OTOG and CACNA1D variants.
Early onset or syndromic epilepsy v1.157 CACNA1D Rebecca Foulger Mode of inheritance for gene: CACNA1D was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital adrenal hypoplasia v1.10 STAR Ivone Leong Phenotypes for gene: STAR were changed from Ideopathic Primary Adrenal Failure; Congenital Adrenal Hypoplasia; Lipoid adrenal hyperplasia to Ideopathic Primary Adrenal Failure; Congenital Adrenal Hypoplasia; Lipoid adrenal hyperplasia, 201710
Congenital adrenal hypoplasia v1.9 CDKN1C Ivone Leong Phenotypes for gene: CDKN1C were changed from Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies (IMAGe syndrome) to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies (IMAGe syndrome), 614732
Congenital adrenal hypoplasia v1.8 AAAS Ivone Leong Phenotypes for gene: AAAS were changed from Triple A syndrome (Addisons, achalasia, alacrima) to Triple A syndrome (Addisons, achalasia, alacrima), 231550
Early onset or syndromic epilepsy v1.156 CACNA1D Rebecca Foulger Publications for gene: CACNA1D were set to 28472301; 23913001
Early onset or syndromic epilepsy v1.155 BSCL2 Rebecca Foulger Publications for gene: BSCL2 were set to 24896178; 26503795; 23564749; 15181077
Intellectual disability v2.951 POU3F3 Konstantinos Varvagiannis gene: POU3F3 was added
gene: POU3F3 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: POU3F3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POU3F3 were set to https://doi.org/10.1016/j.ajhg.2019.06.007; 24550763
Phenotypes for gene: POU3F3 were set to Generalized hypotonia; Delayed speech and language development; Global developmental delay; Intellectual disability; Autistic behavior
Penetrance for gene: POU3F3 were set to unknown
Review for gene: POU3F3 was set to GREEN
gene: POU3F3 was marked as current diagnostic
Added comment: Snijders Blok et al. (2019, DOI: https://doi.org/10.1016/j.ajhg.2019.06.007) report on 19 individuals with heterozygous POU3F3 variants.

Features included hypotonia in some, DD/ID (19/19) with impairment in speech and language skills, and autism-like symptoms with formal ASD diagnosis in 7(/19). Epilepsy was reported for 2 individuals. Overlapping facial features were noted among these individuals.

POU3F3 encodes a member of the class III POU family of transcription factors expressed in the central nervous system (Sumiyama et al. 1996, PMID: 8703082 cited in OMIM) and as the authors comment holds a role in regulation of key processes, eg. cortical neuronal migration, upper-layer specification and production and neurogenesis (PMIDs cited: 11859196, 12130536, 22892427, 17141158).

In almost all subjects (17/19) the variant had occurred as a de novo event, while one individual had inherited the variant from a similarly affected parent.

In total 12 nonsense/frameshift variants, 5 missense ones as well as 1 in-frame deletion were identified following (mostly) trio exome sequencing. All variants were absent from gnomAD, with in silico predictions in favour of pathogenicity.

The few missense variants and the in-frame deletion were found either in the POU-specific (NM_006236.2:c.1085G>T / p.Arg362Leu found in 2 subjects) or the POU-homeobox domain (where 2 variants affected the same residue, namely p.Arg407Gly/Leu, the other variant was p.Asn456Ser).

POU3F3 is an intronless gene and as a result truncating variants are not subject to NMD. The gene appears to be intolerant to LoF variants (pLI of 0.89 in gnomAD).

Western blot analysis of YFP-tagged POU3F3 variants (in HEK293 cell lysates) showed that the YFP-fusion proteins were expressed and had the expected molecular weights.

For several truncating variants tested as well as the in-frame deletion, aberrant subcellular localization pattern was demonstrated although this was not the case for 4 missense variants.

In vitro studies were carried out and suggested that POU3F3, as is known to be the case for POU3F2, is able to activate an intronic binding site in FOXP2. Using a luciferase assay, transcriptional activation was severely impaired for truncating variants tested, significantly lower for many missense ones with the exception of those affecting Arg407 in which case luciferase expression was either similar to wt (for Arg407Gly) or even increased in the case of Arg407Leu.

As the authors comment, both loss- and gain- of function mechanisms may underly pathogenicity of variants.

The ability of mutant proteins to form dimers either with wt or themselves was tested. Dimerization capacity was intact for most missense variants but was lost/decreased for truncating variants. The in-frame deletion resulted in impaired dimerization with wt, although homo-dimerization was found to be normal.
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Dheedene et al. (2014 - PMID: 24550763) had previously reported on a boy with ID. aCGH had demonstrated a de novo 360-kb deletion of 2q12.1 spanning only POU3F3 and MRPS9 the latter encoding a mitochondrial ribosomal protein (which would be most compatible with a - yet undescribed - recessive inheritance pattern / disorder).
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POU3F3 is not associated with any phenotype in OMIM/G2P.
The gene is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc, among the principal authors of the study).
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As a result POU3F3 seems to fulfill criteria for inclusion in the current panel probably as green [DD/ID was a universal feature - severity of ID was relevant in 5/10 individuals for whom details were available, functional evidence provided] or amber.
Sources: Literature, Radboud University Medical Center, Nijmegen
DDG2P v1.78 MYPN Rebecca Foulger changed review comment from: Original DDG2P rating: child IF. DD-G2P rating for Childhood-Onset, Slowly Progressive Nemaline Myopathy: child IF.; to: Original DDG2P rating for Childhood-Onset, Slowly Progressive Nemaline Myopathy: child IF.
DDG2P v1.78 PIH1D3 Rebecca Foulger changed review comment from: Original DDG2P rating: child IF. DDG2P rating for X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects: child IF.; to: Original DDG2P rating for X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects: child IF.
DDG2P v1.78 TMEM199 Rebecca Foulger changed review comment from: Original DDG2P rating: child IF. DDG2P rating for Disorder of Golgi homeostasis: child IF.; to: Original DDG2P rating for Disorder of Golgi homeostasis: child IF.
DDG2P v1.78 TERC Rebecca Foulger changed review comment from: Original DDG2P rating: child IF. DDG2P rating for Dyskeratosis congenita, autosomal dominant 1 : child IF.; to: Original DDG2P rating for Dyskeratosis congenita, autosomal dominant 1: child IF.
DDG2P v1.77 BGN Rebecca Foulger Source Expert Review Green was added to BGN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ANO5 Rebecca Foulger Source Expert Review Green was added to ANO5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 FMR1 Rebecca Foulger Source Expert Review Green was added to FMR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SMAD4 Rebecca Foulger Source Expert Review Green was added to SMAD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 TIMM8A Rebecca Foulger Source Expert Review Green was added to TIMM8A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 THAP1 Rebecca Foulger Source Expert Review Green was added to THAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 TGFB2 Rebecca Foulger Source Expert Review Green was added to TGFB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SYNE1 Rebecca Foulger Source Expert Review Green was added to SYNE1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SPTLC2 Rebecca Foulger Source Expert Review Green was added to SPTLC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SNORD118 Rebecca Foulger Source Expert Review Green was added to SNORD118.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SMCHD1 Rebecca Foulger Source Expert Review Green was added to SMCHD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SLC4A11 Rebecca Foulger Source Expert Review Green was added to SLC4A11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 SLC4A1 Rebecca Foulger Source Expert Review Green was added to SLC4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 RRM2B Rebecca Foulger Source Expert Review Green was added to RRM2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 RET Rebecca Foulger Source Expert Review Green was added to RET.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 POLD1 Rebecca Foulger Source Expert Review Green was added to POLD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 PLA2G6 Rebecca Foulger Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 PDCD10 Rebecca Foulger Source Expert Review Green was added to PDCD10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 NR5A1 Rebecca Foulger Source Expert Review Green was added to NR5A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 MYO7A Rebecca Foulger Source Expert Review Green was added to MYO7A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 MYH8 Rebecca Foulger Source Expert Review Green was added to MYH8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 MYH6 Rebecca Foulger Source Expert Review Green was added to MYH6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 LMNA Rebecca Foulger Source Expert Review Green was added to LMNA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 LDB3 Rebecca Foulger Source Expert Review Green was added to LDB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 KRIT1 Rebecca Foulger Source Expert Review Green was added to KRIT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 KIT Rebecca Foulger Source Expert Review Green was added to KIT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 KARS Rebecca Foulger Source Expert Review Green was added to KARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 HSPD1 Rebecca Foulger Source Expert Review Green was added to HSPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 GJB3 Rebecca Foulger Source Expert Review Green was added to GJB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 GBA Rebecca Foulger Source Expert Review Green was added to GBA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 FAM161A Rebecca Foulger Source Expert Review Green was added to FAM161A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 DARS2 Rebecca Foulger Source Expert Review Green was added to DARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 COL4A2 Rebecca Foulger Source Expert Review Green was added to COL4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 COL4A1 Rebecca Foulger Source Expert Review Green was added to COL4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 CLN6 Rebecca Foulger Source Expert Review Green was added to CLN6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 CISD2 Rebecca Foulger Source Expert Review Green was added to CISD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 CDH1 Rebecca Foulger Source Expert Review Green was added to CDH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 BRCA2 Rebecca Foulger Source Expert Review Green was added to BRCA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 BRCA1 Rebecca Foulger Source Expert Review Green was added to BRCA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ATP1A3 Rebecca Foulger Source Expert Review Green was added to ATP1A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ATP13A2 Rebecca Foulger Source Expert Review Green was added to ATP13A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 AR Rebecca Foulger Source Expert Review Green was added to AR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 AMER1 Rebecca Foulger Source Expert Review Green was added to AMER1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ALDOB Rebecca Foulger Source Expert Review Green was added to ALDOB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ALAD Rebecca Foulger Source Expert Review Green was added to ALAD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 AIRE Rebecca Foulger Source Expert Review Green was added to AIRE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 AGXT Rebecca Foulger Source Expert Review Green was added to AGXT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ACTA2 Rebecca Foulger Source Expert Review Green was added to ACTA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ACADS Rebecca Foulger Source Expert Review Green was added to ACADS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.77 ABCD1 Rebecca Foulger Source Expert Review Green was added to ABCD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v1.76 BGN Rebecca Foulger commented on gene: BGN: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp. BGN also rated 'probable' for X-Linked Spondyloepimetaphyseal Dysplasia.
DDG2P v1.76 ANO5 Rebecca Foulger commented on gene: ANO5: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp. ANO5 also rated 'possible' for LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2L.
DDG2P v1.76 FMR1 Rebecca Foulger commented on gene: FMR1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp. FMR1 also rated 'confirmed' for FRAGILE X SYNDROME.
DDG2P v1.76 SMAD4 Rebecca Foulger commented on gene: SMAD4: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp. SMAD4 also rated 'confirmed' for MYHRE SYNDROME.
DDG2P v1.76 TIMM8A Rebecca Foulger commented on gene: TIMM8A: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 THAP1 Rebecca Foulger commented on gene: THAP1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 TGFB2 Rebecca Foulger commented on gene: TGFB2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 SYNE1 Rebecca Foulger commented on gene: SYNE1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 SPTLC2 Rebecca Foulger commented on gene: SPTLC2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 SNORD118 Rebecca Foulger commented on gene: SNORD118: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 SMCHD1 Rebecca Foulger commented on gene: SMCHD1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 SLC4A11 Rebecca Foulger commented on gene: SLC4A11: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 SLC4A1 Rebecca Foulger commented on gene: SLC4A1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 RRM2B Rebecca Foulger commented on gene: RRM2B: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 RET Rebecca Foulger commented on gene: RET: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 POLD1 Rebecca Foulger commented on gene: POLD1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 PLA2G6 Rebecca Foulger commented on gene: PLA2G6: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 PDCD10 Rebecca Foulger commented on gene: PDCD10: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 NR5A1 Rebecca Foulger commented on gene: NR5A1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 MYO7A Rebecca Foulger commented on gene: MYO7A: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 MYH8 Rebecca Foulger commented on gene: MYH8: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 MYH6 Rebecca Foulger commented on gene: MYH6: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 LMNA Rebecca Foulger commented on gene: LMNA: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 LDB3 Rebecca Foulger commented on gene: LDB3: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 KRIT1 Rebecca Foulger commented on gene: KRIT1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 KIT Rebecca Foulger commented on gene: KIT: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 KARS Rebecca Foulger commented on gene: KARS: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 HSPD1 Rebecca Foulger commented on gene: HSPD1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 GJB3 Rebecca Foulger commented on gene: GJB3: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 GBA Rebecca Foulger commented on gene: GBA: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 FAM161A Rebecca Foulger commented on gene: FAM161A: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 DARS2 Rebecca Foulger commented on gene: DARS2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 COL4A2 Rebecca Foulger commented on gene: COL4A2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 COL4A1 Rebecca Foulger commented on gene: COL4A1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 CLN6 Rebecca Foulger commented on gene: CLN6: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 CISD2 Rebecca Foulger commented on gene: CISD2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 CDH1 Rebecca Foulger commented on gene: CDH1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 BRCA2 Rebecca Foulger commented on gene: BRCA2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 BRCA1 Rebecca Foulger commented on gene: BRCA1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ATP1A3 Rebecca Foulger commented on gene: ATP1A3: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ATP13A2 Rebecca Foulger commented on gene: ATP13A2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 AR Rebecca Foulger commented on gene: AR: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 AMER1 Rebecca Foulger commented on gene: AMER1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ALDOB Rebecca Foulger commented on gene: ALDOB: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ALAD Rebecca Foulger commented on gene: ALAD: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 AIRE Rebecca Foulger commented on gene: AIRE: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 AGXT Rebecca Foulger commented on gene: AGXT: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ACTA2 Rebecca Foulger commented on gene: ACTA2: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ACADS Rebecca Foulger commented on gene: ACADS: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
DDG2P v1.76 ABCD1 Rebecca Foulger commented on gene: ABCD1: Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp.
Fetal anomalies v0.299 GBE1 Anna de Burca Phenotypes for gene: GBE1 were changed from Glycogen storage disease IV; Polyglucosan body disease, adult form to Glycogen storage disease IV; Polyglucosan body disease, adult form; Fetal akinesia deformation sequence
Fetal anomalies v0.298 GBE1 Anna de Burca reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21620786; Phenotypes: Fetal akinesia deformation sequence; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.298 COQ4 Anna de Burca reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25658047; Phenotypes: COENZYME Q10 DEFICIENCY, PRIMARY; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Classified gene: ATP2B2 as Amber List (moderate evidence)
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Gene: atp2b2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.121 ATP2B2 Eleanor Williams Phenotypes for gene: ATP2B2 were changed from to {Deafness, autosomal recessive 12, modifier of} 601386
Monogenic hearing loss v1.120 ATP2B2 Eleanor Williams Added comment: Comment on publications: PMID: 17234811 - Ficarella et al 2007 - A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness.
Monogenic hearing loss v1.120 ATP2B2 Eleanor Williams Publications for gene: ATP2B2 were set to 30535804
Monogenic hearing loss v1.119 ATP2B2 Eleanor Williams Publications for gene: ATP2B2 were set to
Monogenic hearing loss v1.118 ATP2B2 Eleanor Williams Added comment: Comment on mode of inheritance: The 5 cases described in PMID: 30535804 show a monoallelic pattern of inheritance
Monogenic hearing loss v1.118 ATP2B2 Eleanor Williams Mode of inheritance for gene: ATP2B2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.117 ATP2B2 Eleanor Williams edited their review of gene: ATP2B2: Added comment: PMID: 30535804 - Smits et al 2019 - report 5 independant cases. Whole exome sequencing in hearing impaired index cases of Dutch and Polish origins revealed five novel heterozygous (predicted to be) loss-of-function variants of ATP2B2. Two variants, c.1963G>T (p.Glu655*) and c.955delG (p.Ala319fs), occurred de novo. Three variants c.397+1G>A (p.?), c.1998C>A (p.Cys666*), and c.2329C>T (p.Arg777*), were identified in families with an autosomal dominant inheritance pattern of hearing impairment. In most cases HI was early onset, but in one individual hearing loss was reported around 55 years. Whole exome sequence (WES) data were analyzed for variants in a panel of 142 genes known to be associated with nonsyndromic hearing impairment (HI) and relatively common syndromic forms of HI. All variants affect exons, or their splice sites, that encode the ortholog of the rat PMCA2 w/a isoform. This isoform is highly abundant in stereocilia of outer hair cells (OHC) and to a lesser extent at the apical surface of inner hair cells of rats.

Although rare CDH23 variants cooccurred with ATP2B2 variants in all five index cases, they state their findings indicate that mono-allelic loss-of-function variants of ATP2B2 are the underlying cause of HI. However, variants in deep intronic regions or promoter regions were not addressed and can, therefore, not be excluded. CNVs of CDH23 can be excluded for the index cases only. They state they cannot exclude a modifying effect of the CDH23 variants on HI in the affected subjects in their study.; Changed publications: 30535804
Early onset or syndromic epilepsy v1.154 HCN2 Rebecca Foulger changed review comment from: Comment on mode of inheritance: PMID:29064616: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.; to: Comment on mode of inheritance: PMID:22131395: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.
Early onset or syndromic epilepsy v1.154 HCN2 Rebecca Foulger Added comment: Comment on mode of inheritance: PMID:29064616: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.
Early onset or syndromic epilepsy v1.154 HCN2 Rebecca Foulger Mode of inheritance for gene: HCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal ciliopathies v0.6 SUFU Eleanor Williams commented on gene: SUFU
Skeletal ciliopathies v0.6 IFT81 Eleanor Williams Publications for gene: IFT81 were set to 27666822; 26275418
Skeletal ciliopathies v0.5 IFT81 Eleanor Williams commented on gene: IFT81
Skeletal dysplasia v1.166 IFT81 Eleanor Williams Publications for gene: IFT81 were set to 27666822; 26275418; 28460050
Skeletal ciliopathies v0.5 WDPCP Eleanor Williams commented on gene: WDPCP: From OMIM:
?Bardet-Biedl syndrome 15 - no clinical features reported
?Congenital heart defects, hamartomas of tongue, and polysyndactyly - Syndactyly, fingers 2-3 and Postaxial polydactyly
Skeletal ciliopathies v0.5 SDCCAG8 Eleanor Williams commented on gene: SDCCAG8
Skeletal ciliopathies v0.5 MKKS Eleanor Williams commented on gene: MKKS
Undiagnosed metabolic disorders v1.119 SDHB Sarah Leigh Added comment: Comment on phenotypes: Cowden syndrome 2, 612359 has been removed from SDHB as this gene is not associated with this phenotype.
Undiagnosed metabolic disorders v1.119 SDHB Sarah Leigh Phenotypes for gene: SDHB were changed from Complex II (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex II deficiency; Paragangliomas 4, 115310; Pheochromocytoma, 171300; Paraganglioma and gastric stromal sarcoma, 606864; Cowden syndrome 2, 612359; Gastrointestinal stromal tumor, 606764; Mitochondrial Diseases to Complex II (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex II deficiency; Paragangliomas 4, 115310; Pheochromocytoma, 171300; Paraganglioma and gastric stromal sarcoma, 606864; Gastrointestinal stromal tumor, 606764; Mitochondrial Diseases
Skeletal ciliopathies v0.5 BBS9 Eleanor Williams commented on gene: BBS9
Skeletal ciliopathies v0.5 BBS7 Eleanor Williams commented on gene: BBS7
Skeletal ciliopathies v0.5 BBS5 Eleanor Williams commented on gene: BBS5
Skeletal ciliopathies v0.5 BBS4 Eleanor Williams commented on gene: BBS4
Skeletal ciliopathies v0.5 BBS2 Eleanor Williams commented on gene: BBS2
Skeletal ciliopathies v0.5 BBS12 Eleanor Williams commented on gene: BBS12
Skeletal ciliopathies v0.5 BBS10 Eleanor Williams commented on gene: BBS10
Skeletal ciliopathies v0.5 BBS1 Eleanor Williams commented on gene: BBS1
Mitochondrial disorders v1.408 SDHB Sarah Leigh Classified gene: SDHB as Amber List (moderate evidence)
Mitochondrial disorders v1.408 SDHB Sarah Leigh Added comment: Comment on list classification: Demoted from Green to Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019).
Mitochondrial disorders v1.408 SDHB Sarah Leigh Gene: sdhb has been classified as Amber List (Moderate Evidence).
Mitochondrial disorder with complex II deficiency v0.17 SDHB Ivone Leong changed review comment from: Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group. Gene Symbol submitted: NDUFA11; Suggested intial gene rating: Green; Information provided: Mode of inheritance and publication.; to: Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group. Gene Symbol submitted: SDHB; Suggested intial gene rating: Green; Information provided: Mode of inheritance and publication.
Skeletal ciliopathies v0.5 ARL6 Eleanor Williams commented on gene: ARL6
Hyperthyroidism v1.8 ALB Ivone Leong reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: ; Publications: 27834068, 24646103, 8064810, 29163366; Phenotypes: ; Mode of inheritance:
Hyperthyroidism v1.8 TSHR Ivone Leong reviewed gene: TSHR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hyperthyroidism v1.8 TSHR krishna chatterjee reviewed gene: TSHR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital, nonautoimmune hyperthyroidism; Mode of inheritance:
Hyperthyroidism v1.8 THRA krishna chatterjee reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Resistance to Thyroid Hormone alpha; Mode of inheritance:
Hyperthyroidism v1.8 THRB krishna chatterjee reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Resistance to Thyroid Hormone beta; Mode of inheritance:
Hyperthyroidism v1.8 SECISBP2 krishna chatterjee reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Selenoprotein deficiency; Mode of inheritance:
Hyperthyroidism v1.8 SLC16A2 krishna chatterjee reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Allan Herndon Dudley Syndrome; Mode of inheritance:
Hyperthyroidism v1.8 ALB krishna chatterjee reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Familial dysalbuminaemic hyperthyroxinaemia; Mode of inheritance:
Hyperthyroidism v1.7 TSHR Ivone Leong gene: TSHR was added
gene: TSHR was added to Hyperthyroidism. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TSHR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TSHR were set to Congenital, nonautoimmune hyperthyroidism; Hyperthyroidism, nonautoimmune, 609152
Hyperthyroidism v1.7 THRA Ivone Leong Source Expert list was added to THRA.
Hyperthyroidism v1.7 THRB Ivone Leong Source Expert list was added to THRB.
Hyperthyroidism v1.7 SECISBP2 Ivone Leong Source Expert list was added to SECISBP2.
Hyperthyroidism v1.7 SLC16A2 Ivone Leong Source Expert list was added to SLC16A2.
Hyperthyroidism v1.7 ALB Ivone Leong gene: ALB was added
gene: ALB was added to Hyperthyroidism. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: ALB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ALB were set to 29163366; 8064810; 24646103; 27834068
Phenotypes for gene: ALB were set to Familial dysalbuminaemic hyperthyroxinaemia; [Dysalbuminemic hyperthyroxinemia], 615999
Mitochondrial disorders v1.407 SDHB Sarah Leigh Publications for gene: SDHB were set to 26925370; 22972948
Mitochondrial disorders v1.407 SDHB Sarah Leigh Publications for gene: SDHB were set to PMID: 26925370; 22972948
Mitochondrial disorders v1.406 MTPAP Sarah Leigh Phenotypes for gene: MTPAP were changed from Ataxia, spastic, 4, 613672 to ?Spastic ataxia 4, autosomal recessive 613672
Mitochondrial disorders v1.405 MTPAP Sarah Leigh Classified gene: MTPAP as Green List (high evidence)
Mitochondrial disorders v1.405 MTPAP Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in unrelated cases, and supportive functional studies.
Mitochondrial disorders v1.405 MTPAP Sarah Leigh Gene: mtpap has been classified as Green List (High Evidence).
Skeletal ciliopathies v0.4 SUFU Eleanor Williams gene: SUFU was added
gene: SUFU was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: SUFU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUFU were set to 28965847
Phenotypes for gene: SUFU were set to Joubert syndrome 32, 617757
Early onset or syndromic epilepsy v1.153 RELN Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from monoallelic to 'BOTH monoallelic and biallelic' based on papers reporting seizures as part of AR lissencephaly phenotype: PMID:17431900 (Zaki et al 2007) and PMID:10973257 (Hong et al, 2000).
Early onset or syndromic epilepsy v1.153 RELN Rebecca Foulger Mode of inheritance for gene: RELN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset leukodystrophy v0.13 MTHFR Louise Daugherty Publications for gene: MTHFR were set to 27159321; 25527826; 28334938; 20301621; 24357685; 29391032
Adult onset leukodystrophy v0.12 MTHFR Louise Daugherty Publications for gene: MTHFR were set to 27159321; 25527826; 28334938; 20301621; 24357685
Early onset or syndromic epilepsy v1.152 PRICKLE1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from biallelic to BOTH monoallelic and biallelic based on PMID:21276947. Tao et al. 2011 sequenced PRICKLE1 (and PRICKLE2) in 88 unrelated patients with myoclonus epilepsy and found two patients with heterozygous missense mutations in PRICKLE1: p.Arg144His and p.Tyr472His. The variants were not found in control data sets. The authors therefore suggest that the heterozygous PRICKLE1 variants are also associated with myoclonus epilepsy.
Early onset or syndromic epilepsy v1.152 PRICKLE1 Rebecca Foulger Mode of inheritance for gene: PRICKLE1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ophthalmological ciliopathies v0.5 SUFU Ivone Leong gene: SUFU was added
gene: SUFU was added to Ophthalmological ciliopathies. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: SUFU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUFU were set to 28965847
Phenotypes for gene: SUFU were set to Joubert syndrome 32, 617757
Early onset or syndromic epilepsy v1.151 NEXMIF Rebecca Foulger Publications for gene: NEXMIF were set to PMID:23615299
Early onset or syndromic epilepsy v1.150 NEXMIF Rebecca Foulger Phenotypes for gene: NEXMIF were changed from Mental retardation, X-linked 98 to Mental retardation, X-linked 98, 300912
Intellectual disability v2.951 NEXMIF Rebecca Foulger Publications for gene: NEXMIF were set to
Intellectual disability v2.950 NEXMIF Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from XLR to XLD to match the XLD recorded for 'Mental retardation, X-linked 98' in OMIM (MIM:300912) and Gene2Phenotype, which records X-linked dominant inheritance for 'Intellectual disability and epilepsy' in addition to hemizgyous inheritance for 'KIAA2022'. An XLD inheritance is supported by PMID:27358180 which reports 14 female patients who carry a heterozygous de novo NEXMIF (KIAA2022) variant and share a phenotype characterised by intellectual disability and epilepsy.
Intellectual disability v2.950 NEXMIF Rebecca Foulger Mode of inheritance for gene: NEXMIF was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v1.149 NEXMIF Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from XLR to XLD to match the XLD recorded for 'Mental retardation, X-linked 98' in OMIM (MIM:300912) and Gene2Phenotype, which records X-linked dominant inheritance for 'Intellectual disability and epilepsy' in addition to hemizgyous inheritance for 'KIAA2022'. An XLD inheritance is supported by PMID:27358180 which reports 14 female patients who carry a heterozygous de novo KIAA2022 variant and share a phenotype characterised by intellectual disability and epilepsy.
Early onset or syndromic epilepsy v1.149 NEXMIF Rebecca Foulger Mode of inheritance for gene: NEXMIF was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v1.148 CLCN4 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from XLR to XLD to match XLD MOI for 'Raynaud-Claes syndrome' (MIM:300114) in OMIM.
Early onset or syndromic epilepsy v1.148 CLCN4 Rebecca Foulger Mode of inheritance for gene: CLCN4 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Retinal disorders v1.145 REEP6 Ivone Leong Phenotypes for gene: REEP6 were changed from retinitis pigmentosa to retinitis pigmentosa; Retinitis pigmentosa 77, 617304
Retinal disorders v1.144 REEP6 Ivone Leong Publications for gene: REEP6 were set to PMID: 30101608; 28475715; 28369466; 27889058; 24691551
Retinal disorders v1.143 CFH Ivone Leong Classified gene: CFH as Green List (high evidence)
Retinal disorders v1.143 CFH Ivone Leong Added comment: Comment on list classification: Promoted from red to green. CFH is associated with Basal laminar drusen (OMIM:126700) in OMIM but not in Gene2Phenotype. There are >3 unrelated cases in OMIM and therefore there is enough evidence to promote this gene to green status.
Retinal disorders v1.143 CFH Ivone Leong Gene: cfh has been classified as Green List (High Evidence).
Retinal disorders v1.142 CFH Ivone Leong Phenotypes for gene: CFH were changed from {Macular degeneration, age-related, 4} 610698 to {Macular degeneration, age-related, 4} 610698; Basal laminar drusen, 126700
Skeletal ciliopathies v0.1 TBC1D32 Eleanor Williams gene: TBC1D32 was added
gene: TBC1D32 was added to Skeletal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: TBC1D32 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D32 were set to No OMIM phenotype; Oro-facio-digital syndrome type IX (Adly (2014) Hum Mutat 35, 36)
Skeletal ciliopathies v0.1 TAPT1 Eleanor Williams gene: TAPT1 was added
gene: TAPT1 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: TAPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAPT1 were set to 26365339
Phenotypes for gene: TAPT1 were set to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type 616897
Skeletal ciliopathies v0.1 LBR Eleanor Williams gene: LBR was added
gene: LBR was added to Skeletal ciliopathies. Sources: UKGTN,Expert list,Expert Review Red
Mode of inheritance for gene: LBR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LBR were set to Skeletal Ciliopathies
Skeletal ciliopathies v0.1 B9D1 Eleanor Williams gene: B9D1 was added
gene: B9D1 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D1 were set to 21493627 (case report, with an additional variant in the CEP290 gene suggesting oligogenetic inheritance); 24886560 (2 cases with Joubert); 25920555 (report a case with heterozygous mutations in CC2D2A and B9D1)
Phenotypes for gene: B9D1 were set to ?Meckel syndrome 9, 614209; ciliopathies; Meckel syndrome; Joubert syndrome 27
Skeletal ciliopathies v0.1 ZSWIM6 Eleanor Williams gene: ZSWIM6 was added
gene: ZSWIM6 was added to Skeletal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZSWIM6 were set to 25105228
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis 603671
Mode of pathogenicity for gene: ZSWIM6 was set to Other - please provide details in the comments
Skeletal ciliopathies v0.1 WDR60 Eleanor Williams gene: WDR60 was added
gene: WDR60 was added to Skeletal ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: WDR60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR60 were set to 25492405; 23910462; 29271569; 26874042
Phenotypes for gene: WDR60 were set to Short-rib thoracic dysplasia 8 with or without polydactyly, 615503; Short-rib thoracic dysplasia 8 with or without polydactyly; Jeune syndrome; SHORT-RIB POLYDACTYLY
Skeletal ciliopathies v0.1 WDR35 Eleanor Williams gene: WDR35 was added
gene: WDR35 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: WDR35 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR35 were set to Cranioectodermal dysplasia 2, 613610; Cranioectodermal dysplasia; Short-rib thoracic dysplasia 7 with or without polydactyly; Short-rib thoracic dysplasia 7 with or without polydactyly, 614091
Skeletal ciliopathies v0.1 WDR34 Eleanor Williams gene: WDR34 was added
gene: WDR34 was added to Skeletal ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: WDR34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR34 were set to 24183449
Phenotypes for gene: WDR34 were set to Short-rib thoracic dysplasia 11 with or without polydactyly; Jeune syndrome; Short-rib thoracic dysplasia 11 with or without polydactyly, 615633
Skeletal ciliopathies v0.1 WDR19 Eleanor Williams gene: WDR19 was added
gene: WDR19 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: WDR19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR19 were set to Nephronophthisis 13, 614377; ?Short-rib thoracic dysplasia 5 with or without polydactyly; Senior-Loken syndrome 8, 616307; Cranioectodermal dysplasia; ?Short-rib thoracic dysplasia 5 with or without polydactyly, 614376; Jeune syndrome; Senior-Loken syndrome; ?Cranioectodermal dysplasia 4, 614378; Nephronophthisis
Skeletal ciliopathies v0.1 TTC21B Eleanor Williams gene: TTC21B was added
gene: TTC21B was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Orphanet,Expert Review Green
Mode of inheritance for gene: TTC21B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC21B were set to 21258341; 27515926 (functional study in C. elegans); 21068128; 24876116 (Focal segmental glomerulosclerosis)
Phenotypes for gene: TTC21B were set to Nephronophthisis 12, 613820; Short-rib thoracic dysplasia 4 with or without polydactyly; Jeune syndrome; Short-rib thoracic dysplasia 4 with or without polydactyly, 613819; Nephronophthisis
Skeletal ciliopathies v0.1 TCTEX1D2 Eleanor Williams gene: TCTEX1D2 was added
gene: TCTEX1D2 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TCTEX1D2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTEX1D2 were set to 28475963; 25830415; 26044572
Phenotypes for gene: TCTEX1D2 were set to Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; JATD; Jeune asphyxiating thoracic dystrophy
Skeletal ciliopathies v0.1 SCLT1 Eleanor Williams gene: SCLT1 was added
gene: SCLT1 was added to Skeletal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to 28005958; 23348840; 24285566; 30425282; 28486600
Phenotypes for gene: SCLT1 were set to Senior-L ken Syndrome; No OMIM phenotype; Oro-facio-digital syndrome type IX
Skeletal ciliopathies v0.1 SBDS Eleanor Williams gene: SBDS was added
gene: SBDS was added to Skeletal ciliopathies. Sources: UKGTN,Expert list,Expert Review Green
Mode of inheritance for gene: SBDS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SBDS were set to 22554078
Phenotypes for gene: SBDS were set to Skeletal Ciliopathies
Skeletal ciliopathies v0.1 PMM2 Eleanor Williams gene: PMM2 was added
gene: PMM2 was added to Skeletal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 9140401
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia 212065
Skeletal ciliopathies v0.1 NEK1 Eleanor Williams gene: NEK1 was added
gene: NEK1 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: NEK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NEK1 were set to Short-rib thoracic dysplasia 6 with or without polydactyly; Short-rib thoracic dysplasia 6 with or without polydactyly, 263520
Skeletal ciliopathies v0.1 IFT80 Eleanor Williams gene: IFT80 was added
gene: IFT80 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: IFT80 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT80 were set to Short-rib thoracic dysplasia 2 with or without polydactyly; Jeune syndrome; Short-rib thoracic dysplasia 2 with or without polydactyly, 611263
Skeletal ciliopathies v0.1 IFT52 Eleanor Williams gene: IFT52 was added
gene: IFT52 was added to Skeletal ciliopathies. Sources: Other,Expert Review Green
Mode of inheritance for gene: IFT52 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT52 were set to 27466190; 26880018; 30242358
Phenotypes for gene: IFT52 were set to Short-rib thoracic dysplasia 16 with or without polydactyly, 617102
Skeletal ciliopathies v0.1 IFT43 Eleanor Williams gene: IFT43 was added
gene: IFT43 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IFT43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT43 were set to 29896747; 28400947; 26892345; 24027799; 21378380; 22791528
Phenotypes for gene: IFT43 were set to Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome; Short-rib thoracic dysplasia 18 with polydactyly, 617866
Skeletal ciliopathies v0.1 IFT172 Eleanor Williams gene: IFT172 was added
gene: IFT172 was added to Skeletal ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: IFT172 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT172 were set to 24140113
Phenotypes for gene: IFT172 were set to Retinitis pigmentosa 71, 616394; Short-rib thoracic dysplasia 10 with or without polydactyly; Saldino-Mainzer syndrome; Jeune syndrome; Short-rib thoracic dysplasia 10 with or without polydactyly, 615630
Skeletal ciliopathies v0.1 IFT140 Eleanor Williams gene: IFT140 was added
gene: IFT140 was added to Skeletal ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IFT140 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT140 were set to 22503633
Phenotypes for gene: IFT140 were set to Saldino-Mainzer syndrome; Jeune syndrome; Short-rib thoracic dysplasia 9 with or without polydactyly, 266920; Mainzer-Saldino Syndrome; Short-rib thoracic dysplasia 9 with or without polydactyly
Skeletal ciliopathies v0.1 IFT122 Eleanor Williams gene: IFT122 was added
gene: IFT122 was added to Skeletal ciliopathies. Sources: Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IFT122 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT122 were set to 19000668; 24027799; 23826986; 26792575; 24689072; 20493458
Phenotypes for gene: IFT122 were set to Cranioectodermal dysplasia; Cranioectodermal dysplasia 1, 218330
Skeletal ciliopathies v0.1 ICK Eleanor Williams gene: ICK was added
gene: ICK was added to Skeletal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICK were set to 19185282; 27069622; 27466187
Phenotypes for gene: ICK were set to short-rib thoracic dysplasia with polydactyly (SRTD); Endocrine-cerebroosteodysplasia, 612651; ECO
Skeletal ciliopathies v0.1 EVC2 Eleanor Williams gene: EVC2 was added
gene: EVC2 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: EVC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EVC2 were set to Ellis-van Creveld syndrome, 225500; Weyers acrofacial dysostosis, 193530
Skeletal ciliopathies v0.1 EVC Eleanor Williams gene: EVC was added
gene: EVC was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: EVC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EVC were set to Ellis-van Creveld syndrome, 225500; Weyers acrodental dysostosis, 193530
Skeletal ciliopathies v0.1 DYNC2LI1 Eleanor Williams gene: DYNC2LI1 was added
gene: DYNC2LI1 was added to Skeletal ciliopathies. Sources: Other,Expert Review Green
Mode of inheritance for gene: DYNC2LI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC2LI1 were set to 26077881
Phenotypes for gene: DYNC2LI1 were set to Short-rib throacic dysplasia 15 with polydactyly, 617088
Skeletal ciliopathies v0.1 DYNC2H1 Eleanor Williams gene: DYNC2H1 was added
gene: DYNC2H1 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: DYNC2H1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DYNC2H1 were set to Short-rib thoracic dysplasia 3 with or without polydactyly; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091
Skeletal ciliopathies v0.1 DHCR7 Eleanor Williams gene: DHCR7 was added
gene: DHCR7 was added to Skeletal ciliopathies. Sources: UKGTN,Expert Review Green
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 9634533
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome 270400
Skeletal ciliopathies v0.1 CEP120 Eleanor Williams gene: CEP120 was added
gene: CEP120 was added to Skeletal ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP120 were set to 29847808
Phenotypes for gene: CEP120 were set to Short-rib thoracic dysplasia 13 with or without polydactyly; Jeune syndrome; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Short-rib thoracic dysplasia 13 with or without polydactyly, 616300
Skeletal ciliopathies v0.1 C2CD3 Eleanor Williams gene: C2CD3 was added
gene: C2CD3 was added to Skeletal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: C2CD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2CD3 were set to 24997988; 26044959; 27094867
Phenotypes for gene: C2CD3 were set to short-rib polydactyly syndromes (SRPS; MIM208500); MIM 613091, 263520), Jeune asphyxiating thoracic dystrophy (JATD; ?Orofaciodigital syndrome XIV, 615948; Orofaciodigital syndromes (OFDS, MIM 311200)
Skeletal ciliopathies v0.1 C21orf2 Eleanor Williams gene: C21orf2 was added
gene: C21orf2 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: C21orf2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C21orf2 were set to 26974433; 27548899; 23105016; 26167768
Phenotypes for gene: C21orf2 were set to Jeune asphyxiating thoracic dystrophy (JATD); Jeune Syndrome; Spondylometaphyseal dysplasia, axial, 602271; Retinal dystrophy with macular staphyloma, 617547
Skeletal ciliopathies v0.1 IFT81 Eleanor Williams gene: IFT81 was added
gene: IFT81 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: IFT81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT81 were set to 27666822; 26275418
Phenotypes for gene: IFT81 were set to Short-rib thoracic dysplasia 19 with or without polydactyly, 617895
Skeletal ciliopathies v0.1 IFT27 Eleanor Williams gene: IFT27 was added
gene: IFT27 was added to Skeletal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Amber
Mode of inheritance for gene: IFT27 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT27 were set to ?Bardet-Biedl syndrome 19, 615996
Skeletal ciliopathies v0.1 TRIM32 Eleanor Williams gene: TRIM32 was added
gene: TRIM32 was added to Skeletal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list,Expert Review Red,UKGTN
Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM32 were set to 11822024; 16606853
Phenotypes for gene: TRIM32 were set to ?Bardet-Biedl syndrome 11, 615988; Muscular dystrophy, limb-girdle, type 2H, 254110
Skeletal ciliopathies v0.1 IFT74 Eleanor Williams gene: IFT74 was added
gene: IFT74 was added to Skeletal ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 27486776
Phenotypes for gene: IFT74 were set to ?Bardet-Biedl syndrome 20, 617119
Skeletal ciliopathies v0.1 CCDC28B Eleanor Williams gene: CCDC28B was added
gene: CCDC28B was added to Skeletal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list,Expert Review Red,UKGTN
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 23015189
Phenotypes for gene: CCDC28B were set to ciliopathies; {Bardet-Biedl syndrome 1, modifier of}, 209900
Skeletal ciliopathies v0.1 C8orf37 Eleanor Williams gene: C8orf37 was added
gene: C8orf37 was added to Skeletal ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C8orf37 were set to 26854863; 27008867
Phenotypes for gene: C8orf37 were set to Bardet-Biedl syndrome 21, 617406
Skeletal ciliopathies v0.1 BBIP1 Eleanor Williams gene: BBIP1 was added
gene: BBIP1 was added to Skeletal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: BBIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBIP1 were set to 24026985
Phenotypes for gene: BBIP1 were set to ?Bardet-Biedl syndrome 18, 615995
Skeletal ciliopathies v0.1 WDPCP Eleanor Williams gene: WDPCP was added
gene: WDPCP was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: WDPCP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDPCP were set to 20671153
Phenotypes for gene: WDPCP were set to ?Bardet-Biedl syndrome 15, 615992; Meckel syndrome; ?Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Skeletal ciliopathies v0.1 TXNDC15 Eleanor Williams gene: TXNDC15 was added
gene: TXNDC15 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNDC15 were set to 27894351
Phenotypes for gene: TXNDC15 were set to MGS; Meckel-Gruber syndrome
Skeletal ciliopathies v0.1 TTC8 Eleanor Williams gene: TTC8 was added
gene: TTC8 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC8 were set to 14520415
Phenotypes for gene: TTC8 were set to Bardet Biedl syndrome 8
Skeletal ciliopathies v0.1 SDCCAG8 Eleanor Williams gene: SDCCAG8 was added
gene: SDCCAG8 was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: SDCCAG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDCCAG8 were set to 22190896
Phenotypes for gene: SDCCAG8 were set to SENIOR-LOKEN SYNDROME; Bardet-Biedl Syndrome; 613615; Senior-Loken syndrome
Skeletal ciliopathies v0.1 MKS1 Eleanor Williams gene: MKS1 was added
gene: MKS1 was added to Skeletal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: MKS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKS1 were set to 26490104; 17437276; 18327255; 24886560; 16415886
Phenotypes for gene: MKS1 were set to occipital encephalocele; Joubert syndrome; Bardet-Biedl syndrome; Joubert syndrome 28; 249000; polydactyly; polycystic kidneys; Meckel-Gruber syndrome; Meckel syndrome; renal fibrosis
Mode of pathogenicity for gene: MKS1 was set to Other - please provide details in the comments
Skeletal ciliopathies v0.1 MKKS Eleanor Williams gene: MKKS was added
gene: MKKS was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: MKKS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKKS were set to 10802661; 10973251; 10973238
Phenotypes for gene: MKKS were set to Bardet Biedl syndrome 6; 236700
Skeletal ciliopathies v0.1 LZTFL1 Eleanor Williams gene: LZTFL1 was added
gene: LZTFL1 was added to Skeletal ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 27312011; 23692385
Phenotypes for gene: LZTFL1 were set to Bardet-Biedl syndrome 17, 615994
Skeletal ciliopathies v0.1 KIAA0753 Eleanor Williams gene: KIAA0753 was added
gene: KIAA0753 was added to Skeletal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0753 were set to 29138412; 28220259; 26643951
Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome; Short-rib skeletal dysplasia
Skeletal ciliopathies v0.1 GLI3 Eleanor Williams gene: GLI3 was added
gene: GLI3 was added to Skeletal ciliopathies. Sources: UKGTN,Expert list,Expert Review Green
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GLI3 were set to Joubert Syndrome and Senior-Loken Syndrome 24 gene panel
Skeletal ciliopathies v0.1 DDX59 Eleanor Williams gene: DDX59 was added
gene: DDX59 was added to Skeletal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to 29127725; 23972372; 28711741
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, 174300
Skeletal ciliopathies v0.1 CENPF Eleanor Williams gene: CENPF was added
gene: CENPF was added to Skeletal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to 26820108
Phenotypes for gene: CENPF were set to Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Skeletal ciliopathies v0.1 BBS9 Eleanor Williams gene: BBS9 was added
gene: BBS9 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS9 were set to 16380913
Phenotypes for gene: BBS9 were set to Bardet Biedl syndrome 9
Skeletal ciliopathies v0.1 BBS7 Eleanor Williams gene: BBS7 was added
gene: BBS7 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS7 were set to 12567324
Phenotypes for gene: BBS7 were set to Bardet Biedl syndrome 7
Skeletal ciliopathies v0.1 BBS5 Eleanor Williams gene: BBS5 was added
gene: BBS5 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS5 were set to 15137946
Phenotypes for gene: BBS5 were set to Bardet Biedl syndrome 5
Skeletal ciliopathies v0.1 BBS4 Eleanor Williams gene: BBS4 was added
gene: BBS4 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS4 were set to 11381270; 22353939
Phenotypes for gene: BBS4 were set to Bardet Biedl syndrome 4
Skeletal ciliopathies v0.1 BBS2 Eleanor Williams gene: BBS2 was added
gene: BBS2 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS2 were set to 11285252
Phenotypes for gene: BBS2 were set to Bardet Biedl syndrome 2
Skeletal ciliopathies v0.1 BBS12 Eleanor Williams gene: BBS12 was added
gene: BBS12 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS12 were set to 17160889
Phenotypes for gene: BBS12 were set to Bardet Biedl syndrome 12
Skeletal ciliopathies v0.1 BBS10 Eleanor Williams gene: BBS10 was added
gene: BBS10 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS10 were set to 16582908
Phenotypes for gene: BBS10 were set to Bardet Biedl syndrome 10
Skeletal ciliopathies v0.1 BBS1 Eleanor Williams gene: BBS1 was added
gene: BBS1 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS1 were set to 23143442; 12118255
Phenotypes for gene: BBS1 were set to Bardet Biedl syndrome 13; 268000; Bardet Biedl syndrome 1; Bardet Biedl syndrome 11
Skeletal ciliopathies v0.1 ARL6 Eleanor Williams gene: ARL6 was added
gene: ARL6 was added to Skeletal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: ARL6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6 were set to 15258860; 21282186
Phenotypes for gene: ARL6 were set to {Bardet Biedl syndrome 1, modifier of}; Bardet-Biedl Syndrome; 268000; Bardet Biedl syndrome 3
Cystic renal disease v1.56 Eleanor Williams Changed child panels to: Cystic kidney disease; Renal ciliopathies
Cystic renal disease v1.55 Eleanor Williams Changed child panels to: Rare multisystem ciliopathy disorders; Cystic kidney disease; Renal ciliopathies
Renal ciliopathies v0.3 Eleanor Williams Panel status changed from internal to public
Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel
Renal ciliopathies v0.1 XPNPEP3 Eleanor Williams gene: XPNPEP3 was added
gene: XPNPEP3 was added to Renal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Orphanet,Expert Review Red,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to 20179356
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis; Ciliopathies; Nephronophthisis-like nephropathy 1, 613159
Renal ciliopathies v0.1 UMOD Eleanor Williams gene: UMOD was added
gene: UMOD was added to Renal ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Expert Review Red
Mode of inheritance for gene: UMOD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: UMOD were set to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel
Renal ciliopathies v0.1 TRIM32 Eleanor Williams gene: TRIM32 was added
gene: TRIM32 was added to Renal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list,Expert Review Red,UKGTN
Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM32 were set to 11822024; 16606853
Phenotypes for gene: TRIM32 were set to ?Bardet-Biedl syndrome 11, 615988; Muscular dystrophy, limb-girdle, type 2H, 254110
Renal ciliopathies v0.1 SEC63 Eleanor Williams gene: SEC63 was added
gene: SEC63 was added to Renal ciliopathies. Sources: UKGTN,Expert list,Expert Review Red
Mode of inheritance for gene: SEC63 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SEC63 were set to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel
Renal ciliopathies v0.1 PIBF1 Eleanor Williams gene: PIBF1 was added
gene: PIBF1 was added to Renal ciliopathies. Sources: Research,Literature,Expert Review Red,Expert Review
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768
Phenotypes for gene: PIBF1 were set to Joubert syndrome; ataxia; vermis hypoplasia; developmental delay; thick superior cerebellar peduncles; superior cerebellar dysplasia
Renal ciliopathies v0.1 PDE6D Eleanor Williams gene: PDE6D was added
gene: PDE6D was added to Renal ciliopathies. Sources: UKGTN,Other,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: PDE6D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6D were set to 24166846
Phenotypes for gene: PDE6D were set to ?Joubert syndrome 22; Joubert Syndrome and Senior-Loken Syndrome 24 gene panel; ?Joubert syndrome 22, 615665
Renal ciliopathies v0.1 MUC1 Eleanor Williams gene: MUC1 was added
gene: MUC1 was added to Renal ciliopathies. Sources: UKGTN,Expert list,Expert Review Red
Mode of inheritance for gene: MUC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MUC1 were set to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel
Renal ciliopathies v0.1 KIF14 Eleanor Williams gene: KIF14 was added
gene: KIF14 was added to Renal ciliopathies. Sources: Other,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red,Orphanet
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to 24128419
Phenotypes for gene: KIF14 were set to ?Meckel syndrome 12, 616258; complex brain malformation; ?Meckel syndrome 12; intrauterine growth restriction (IUGR); microcephaly; Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome; genitourinary malformation; renal cystic dysplasia/agenesis
Renal ciliopathies v0.1 KIAA0556 Eleanor Williams gene: KIAA0556 was added
gene: KIAA0556 was added to Renal ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KIAA0556 were set to ?Joubert syndrome 26
Renal ciliopathies v0.1 IFT74 Eleanor Williams gene: IFT74 was added
gene: IFT74 was added to Renal ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 27486776
Phenotypes for gene: IFT74 were set to ?Bardet-Biedl syndrome 20, 617119
Renal ciliopathies v0.1 EXOC8 Eleanor Williams gene: EXOC8 was added
gene: EXOC8 was added to Renal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert Review Red
Mode of inheritance for gene: EXOC8 was set to
Publications for gene: EXOC8 were set to 22700954
Phenotypes for gene: EXOC8 were set to No OMIM phenotype; Joubert syndrome (Dixon-Salazar (2012) Sci Transl Med 4, 138ra78)
Renal ciliopathies v0.1 EXOC3L2 Eleanor Williams gene: EXOC3L2 was added
gene: EXOC3L2 was added to Renal ciliopathies. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: EXOC3L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC3L2 were set to 28749478; 27894351
Phenotypes for gene: EXOC3L2 were set to Dandy-Walker malformation; enlarged echogenic kidneys; echogenic kidneys; hydrocephalus; anhydramnios
Renal ciliopathies v0.1 DCDC2 Eleanor Williams gene: DCDC2 was added
gene: DCDC2 was added to Renal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red,Orphanet
Mode of inheritance for gene: DCDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCDC2 were set to 25557784 - in vitro/in vivo evidence; 22558177 - expression data for the transcriptome of ciliated cells; 27319779 - biallelic missense variants reported in four affected children with Neonatal sclerosing cholangitis; 27469900 - 7 out of 24 patients with 7 with biallelic protein-truncating variants in DCDC2 (6 of 19 families)
Phenotypes for gene: DCDC2 were set to Neonatal sclerosing cholangitis; Nephronophthisis 19, 616217
Renal ciliopathies v0.1 CCDC28B Eleanor Williams gene: CCDC28B was added
gene: CCDC28B was added to Renal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list,Expert Review Red,UKGTN
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 23015189
Phenotypes for gene: CCDC28B were set to ciliopathies; {Bardet-Biedl syndrome 1, modifier of}, 209900
Renal ciliopathies v0.1 C8orf37 Eleanor Williams gene: C8orf37 was added
gene: C8orf37 was added to Renal ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C8orf37 were set to 26854863; 27008867
Phenotypes for gene: C8orf37 were set to Bardet-Biedl syndrome 21, 617406
Renal ciliopathies v0.1 BBIP1 Eleanor Williams gene: BBIP1 was added
gene: BBIP1 was added to Renal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: BBIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBIP1 were set to 24026985
Phenotypes for gene: BBIP1 were set to ?Bardet-Biedl syndrome 18, 615995
Renal ciliopathies v0.1 B9D1 Eleanor Williams gene: B9D1 was added
gene: B9D1 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D1 were set to 21493627 (case report, with an additional variant in the CEP290 gene suggesting oligogenetic inheritance); 24886560 (2 cases with Joubert); 25920555 (report a case with heterozygous mutations in CC2D2A and B9D1)
Phenotypes for gene: B9D1 were set to ?Meckel syndrome 9, 614209; ciliopathies; Meckel syndrome; Joubert syndrome 27
Renal ciliopathies v0.1 ISCA-37432-Loss Eleanor Williams Region: ISCA-37432-Loss was added
Region: ISCA-37432-Loss was added to Renal ciliopathies. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37432-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37432-Loss were set to Schizophrenia; Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females; delayed development, intellectual disability; 614527; RCAD syndrome; utero-vaginal atresia; Chromosome 17q12 deletion syndrome; Autism Spectrum Disorder; global developmental delay; Renal cysts and diabetes syndrome
Renal ciliopathies v0.1 ISCA-37405-Loss Eleanor Williams Region: ISCA-37405-Loss was added
Region: ISCA-37405-Loss was added to Renal ciliopathies. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37405-Loss was set to BIALLELIC, autosomal or pseudoautosomal
Publications for Region: ISCA-37405-Loss were set to 8852662; 9856524; 15138899
Phenotypes for Region: ISCA-37405-Loss were set to 609583; juvenile nephronophthisis 1: including growth retardation. Joubert syndrome: multisystem disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (resulting in the 'molar tooth sign,' or MTS, on axial MRI), mental retardation, hypotonia, irregular breathing pattern, and eye movement abnormalities; 266900
Renal ciliopathies v0.1 WDR60 Eleanor Williams gene: WDR60 was added
gene: WDR60 was added to Renal ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: WDR60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR60 were set to 25492405; 23910462; 29271569; 26874042
Phenotypes for gene: WDR60 were set to Short-rib thoracic dysplasia 8 with or without polydactyly, 615503; Short-rib thoracic dysplasia 8 with or without polydactyly; Jeune syndrome; SHORT-RIB POLYDACTYLY
Renal ciliopathies v0.1 WDR35 Eleanor Williams gene: WDR35 was added
gene: WDR35 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: WDR35 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR35 were set to Cranioectodermal dysplasia 2, 613610; Cranioectodermal dysplasia; Short-rib thoracic dysplasia 7 with or without polydactyly; Short-rib thoracic dysplasia 7 with or without polydactyly, 614091
Renal ciliopathies v0.1 WDR19 Eleanor Williams gene: WDR19 was added
gene: WDR19 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: WDR19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR19 were set to Nephronophthisis 13, 614377; ?Short-rib thoracic dysplasia 5 with or without polydactyly; Senior-Loken syndrome 8, 616307; Cranioectodermal dysplasia; ?Short-rib thoracic dysplasia 5 with or without polydactyly, 614376; Jeune syndrome; Senior-Loken syndrome; ?Cranioectodermal dysplasia 4, 614378; Nephronophthisis
Renal ciliopathies v0.1 WDPCP Eleanor Williams gene: WDPCP was added
gene: WDPCP was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: WDPCP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDPCP were set to 20671153
Phenotypes for gene: WDPCP were set to ?Bardet-Biedl syndrome 15, 615992; Meckel syndrome; ?Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Renal ciliopathies v0.1 TXNDC15 Eleanor Williams gene: TXNDC15 was added
gene: TXNDC15 was added to Renal ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNDC15 were set to 27894351
Phenotypes for gene: TXNDC15 were set to MGS; Meckel-Gruber syndrome
Renal ciliopathies v0.1 TTC8 Eleanor Williams gene: TTC8 was added
gene: TTC8 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC8 were set to 14520415
Phenotypes for gene: TTC8 were set to Bardet Biedl syndrome 8
Renal ciliopathies v0.1 TTC21B Eleanor Williams gene: TTC21B was added
gene: TTC21B was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Orphanet,Expert Review Green
Mode of inheritance for gene: TTC21B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC21B were set to 21258341; 27515926 (functional study in C. elegans); 21068128; 24876116 (Focal segmental glomerulosclerosis)
Phenotypes for gene: TTC21B were set to Nephronophthisis 12, 613820; Short-rib thoracic dysplasia 4 with or without polydactyly; Jeune syndrome; Short-rib thoracic dysplasia 4 with or without polydactyly, 613819; Nephronophthisis
Renal ciliopathies v0.1 TRAF3IP1 Eleanor Williams gene: TRAF3IP1 was added
gene: TRAF3IP1 was added to Renal ciliopathies. Sources: Orphanet,Expert Review Green
Mode of inheritance for gene: TRAF3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAF3IP1 were set to 26487268
Phenotypes for gene: TRAF3IP1 were set to Senior-Loken syndrome 9 616629
Renal ciliopathies v0.1 TMEM67 Eleanor Williams gene: TMEM67 was added
gene: TMEM67 was added to Renal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: TMEM67 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM67 were set to PMID: 16415887; PMID: 17160906; PMID: 19058225; PMID: 19508969; PMID: 20607301; PMID: 18327255
Phenotypes for gene: TMEM67 were set to Joubert syndrome; nephronophthisis; COACH syndrome; Joubert syndrome 6; ?Bardet-Biedl syndrome?; Senior-Boichis syndrome; 613550; 607361; Meckel-Gruber syndrome; Meckel syndrome; 610688; Nephronophthisis 11; 216360
Renal ciliopathies v0.1 TMEM237 Eleanor Williams gene: TMEM237 was added
gene: TMEM237 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TMEM237 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM237 were set to 22152675; 20301500
Phenotypes for gene: TMEM237 were set to Joubert syndrome; Joubert syndrome with oculorenal defect; Joubert syndrome 14
Renal ciliopathies v0.1 TMEM231 Eleanor Williams gene: TMEM231 was added
gene: TMEM231 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: TMEM231 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM231 were set to Meckel syndrome; Joubert syndrome 20; Joubert syndrome with oculorenal defect; Joubert syndrome 20, 614970; Meckel syndrome 11, 615397
Renal ciliopathies v0.1 TMEM216 Eleanor Williams gene: TMEM216 was added
gene: TMEM216 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TMEM216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM216 were set to 22282472; 20036350; 20512146
Phenotypes for gene: TMEM216 were set to Joubert syndrome: Meckel-Gruber syndrome; Joubert syndrome with oculorenal defect; Meckel syndrome; Joubert syndrome 2
Renal ciliopathies v0.1 TMEM138 Eleanor Williams gene: TMEM138 was added
gene: TMEM138 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TMEM138 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM138 were set to 22282472
Phenotypes for gene: TMEM138 were set to Joubert syndrome with oculorenal defect; Joubert syndrome 16
Renal ciliopathies v0.1 TMEM107 Eleanor Williams gene: TMEM107 was added
gene: TMEM107 was added to Renal ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM107 were set to 26518474; 26123494; 22698544; 26595381
Phenotypes for gene: TMEM107 were set to Meckel syndrome 13 617562; ?Joubert syndrome 29 617562; Orofaciodigital syndrome XVI 617563
Renal ciliopathies v0.1 TCTN3 Eleanor Williams gene: TCTN3 was added
gene: TCTN3 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTN3 were set to 25118024; 22883145
Phenotypes for gene: TCTN3 were set to Joubert syndrome; Orofaciodigital syndrome IV; Joubert syndrome 18; Meckel-Gruber; Mohr-Majewski syndrome
Renal ciliopathies v0.1 TCTN2 Eleanor Williams gene: TCTN2 was added
gene: TCTN2 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TCTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTN2 were set to 25118024; 21565611
Phenotypes for gene: TCTN2 were set to Meckel syndrome; Joubert syndrome 24; Joubert syndrome, Meckel-Gruber syndrome
Renal ciliopathies v0.1 TCTN1 Eleanor Williams gene: TCTN1 was added
gene: TCTN1 was added to Renal ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TCTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTN1 were set to 20301500; 22693042; 26489806; 21725307; 26477546; 28631893
Phenotypes for gene: TCTN1 were set to Joubert syndrome
Renal ciliopathies v0.1 SDCCAG8 Eleanor Williams gene: SDCCAG8 was added
gene: SDCCAG8 was added to Renal ciliopathies. Sources: Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: SDCCAG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDCCAG8 were set to 22190896
Phenotypes for gene: SDCCAG8 were set to SENIOR-LOKEN SYNDROME; Bardet-Biedl Syndrome; 613615; Senior-Loken syndrome
Renal ciliopathies v0.1 RPGRIP1L Eleanor Williams gene: RPGRIP1L was added
gene: RPGRIP1L was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: RPGRIP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPGRIP1L were set to 17558409; 17558407; 19574260
Phenotypes for gene: RPGRIP1L were set to Joubert syndrome 7; Meckel syndrome 5; Joubert syndrome; Meckel syndrome; Meckel-Gruber syndrome
Renal ciliopathies v0.1 PMM2 Eleanor Williams gene: PMM2 was added
gene: PMM2 was added to Renal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 9140401
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia 212065
Renal ciliopathies v0.1 PKHD1 Eleanor Williams gene: PKHD1 was added
gene: PKHD1 was added to Renal ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: PKHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PKHD1 were set to Polycystic kidney and hepatic disease, 263200
Renal ciliopathies v0.1 PKD2 Eleanor Williams gene: PKD2 was added
gene: PKD2 was added to Renal ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: PKD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PKD2 were set to Polycystic kidney disease 2, 613095
Renal ciliopathies v0.1 PKD1 Eleanor Williams gene: PKD1 was added
gene: PKD1 was added to Renal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: PKD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PKD1 were set to 23624871; 20558538
Phenotypes for gene: PKD1 were set to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Renal ciliopathies v0.1 OFD1 Eleanor Williams gene: OFD1 was added
gene: OFD1 was added to Renal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: OFD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: OFD1 were set to 19800048; 22353940
Phenotypes for gene: OFD1 were set to Joubert syndrome 10; X-linked Joubert syndrome; Orofaciodigital syndrome I
Renal ciliopathies v0.1 NPHP4 Eleanor Williams gene: NPHP4 was added
gene: NPHP4 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NPHP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP4 were set to Senior-Loken syndrome; Nephronophthisis; Senior-Loken syndrome 4, 606996; Nephronophthisis 4, 606966
Renal ciliopathies v0.1 NPHP3 Eleanor Williams gene: NPHP3 was added
gene: NPHP3 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NPHP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP3 were set to Renal-hepatic-pancreatic dysplasia; Senior-Loken syndrome; Nephronophthisis 3, 604387; Meckel syndrome 7, 267010; Renal-hepatic-pancreatic dysplasia 1, 208540; Nephronophthisis
Renal ciliopathies v0.1 NPHP1 Eleanor Williams gene: NPHP1 was added
gene: NPHP1 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NPHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPHP1 were set to 15138899; 22982934; 15689444
Phenotypes for gene: NPHP1 were set to Joubert syndrome 4; Senior-Loken syndrome; 256100 Senior-Loken syndrome-1, 266900; 609583 Nephronophthisis 1, juvenile; Nephronophthisis
Renal ciliopathies v0.1 NEK8 Eleanor Williams gene: NEK8 was added
gene: NEK8 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NEK8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK8 were set to 18199800; 26967905; 26862157; 26697755; 23418306
Phenotypes for gene: NEK8 were set to Renal-hepatic-pancreatic dysplasia; ?Renal-hepatic-pancreatic dysplasia 2, 615415; Nephronophthisis; ?Nephronophthisis 9, 613824
Renal ciliopathies v0.1 MKS1 Eleanor Williams gene: MKS1 was added
gene: MKS1 was added to Renal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: MKS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKS1 were set to 26490104; 17437276; 18327255; 24886560; 16415886
Phenotypes for gene: MKS1 were set to occipital encephalocele; Joubert syndrome; Bardet-Biedl syndrome; Joubert syndrome 28; 249000; polydactyly; polycystic kidneys; Meckel-Gruber syndrome; Meckel syndrome; renal fibrosis
Mode of pathogenicity for gene: MKS1 was set to Other - please provide details in the comments
Renal ciliopathies v0.1 MKKS Eleanor Williams gene: MKKS was added
gene: MKKS was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: MKKS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKKS were set to 10802661; 10973251; 10973238
Phenotypes for gene: MKKS were set to Bardet Biedl syndrome 6; 236700
Renal ciliopathies v0.1 MAPKBP1 Eleanor Williams gene: MAPKBP1 was added
gene: MAPKBP1 was added to Renal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: MAPKBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPKBP1 were set to 28089251
Phenotypes for gene: MAPKBP1 were set to Nephronophthisis 20 617271
Renal ciliopathies v0.1 LZTFL1 Eleanor Williams gene: LZTFL1 was added
gene: LZTFL1 was added to Renal ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 27312011; 23692385
Phenotypes for gene: LZTFL1 were set to Bardet-Biedl syndrome 17, 615994
Renal ciliopathies v0.1 KIF7 Eleanor Williams gene: KIF7 was added
gene: KIF7 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: KIF7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF7 were set to 21633164
Phenotypes for gene: KIF7 were set to Joubert syndrome 12 200990; Acrocallosal syndrome 200990
Renal ciliopathies v0.1 KIAA0753 Eleanor Williams gene: KIAA0753 was added
gene: KIAA0753 was added to Renal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0753 were set to 29138412; 28220259; 26643951
Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome; Short-rib skeletal dysplasia
Renal ciliopathies v0.1 KIAA0586 Eleanor Williams gene: KIAA0586 was added
gene: KIAA0586 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to 26096313
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23; Joubert syndrome; Short-rib thoracic dysplasia 14 with polydactyly; Short-rib dysplasia 14 with polydactyly
Renal ciliopathies v0.1 IQCB1 Eleanor Williams gene: IQCB1 was added
gene: IQCB1 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IQCB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IQCB1 were set to Senior-Loken syndrome 5, 609254; Senior-Loken syndrome
Renal ciliopathies v0.1 INVS Eleanor Williams gene: INVS was added
gene: INVS was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: INVS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INVS were set to 12872123
Phenotypes for gene: INVS were set to Senior-Loken syndrome; Nephronophthisis 2, infantile, 602088; Nephronophthisis
Renal ciliopathies v0.1 INPP5E Eleanor Williams gene: INPP5E was added
gene: INPP5E was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: INPP5E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP5E were set to 23386033; 26748598
Phenotypes for gene: INPP5E were set to Joubert syndrome; Joubert syndrome 1
Renal ciliopathies v0.1 IFT43 Eleanor Williams gene: IFT43 was added
gene: IFT43 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IFT43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT43 were set to 29896747; 28400947; 26892345; 24027799; 21378380; 22791528
Phenotypes for gene: IFT43 were set to Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome; Short-rib thoracic dysplasia 18 with polydactyly, 617866
Renal ciliopathies v0.1 IFT122 Eleanor Williams gene: IFT122 was added
gene: IFT122 was added to Renal ciliopathies. Sources: Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IFT122 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT122 were set to 19000668; 24027799; 23826986; 26792575; 24689072; 20493458
Phenotypes for gene: IFT122 were set to Cranioectodermal dysplasia; Cranioectodermal dysplasia 1, 218330
Renal ciliopathies v0.1 ICK Eleanor Williams gene: ICK was added
gene: ICK was added to Renal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICK were set to 19185282; 27069622; 27466187
Phenotypes for gene: ICK were set to short-rib thoracic dysplasia with polydactyly (SRTD); Endocrine-cerebroosteodysplasia, 612651; ECO
Renal ciliopathies v0.1 HYLS1 Eleanor Williams gene: HYLS1 was added
gene: HYLS1 was added to Renal ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: HYLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYLS1 were set to 26830932 - report in two siblings with Joubert syndrome; 19656802 - impairment in ciligenesis; 18648327 - Hydrolethalus syndrome; 15843405 - Hydrolethalus syndrome
Phenotypes for gene: HYLS1 were set to Joubert syndrome; Hydrolethalus syndrome, 236680
Renal ciliopathies v0.1 HNF1B Eleanor Williams gene: HNF1B was added
gene: HNF1B was added to Renal ciliopathies. Sources: UKGTN,Expert list,Expert Review Green
Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HNF1B were set to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel
Renal ciliopathies v0.1 DYNC2H1 Eleanor Williams gene: DYNC2H1 was added
gene: DYNC2H1 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: DYNC2H1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DYNC2H1 were set to Short-rib thoracic dysplasia 3 with or without polydactyly; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091
Renal ciliopathies v0.1 DHCR7 Eleanor Williams gene: DHCR7 was added
gene: DHCR7 was added to Renal ciliopathies. Sources: UKGTN,Expert Review Green
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 9634533
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome 270400
Renal ciliopathies v0.1 DDX59 Eleanor Williams gene: DDX59 was added
gene: DDX59 was added to Renal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to 29127725; 23972372; 28711741
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, 174300
Renal ciliopathies v0.1 CSPP1 Eleanor Williams gene: CSPP1 was added
gene: CSPP1 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: CSPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSPP1 were set to 24360807; 24360803; 24360808
Phenotypes for gene: CSPP1 were set to Joubert syndrome; Meckel syndrome; Joubert syndrome 21; Meckel-Gruber syndrome
Renal ciliopathies v0.1 CRB2 Eleanor Williams gene: CRB2 was added
gene: CRB2 was added to Renal ciliopathies. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: CRB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRB2 were set to 25557780
Phenotypes for gene: CRB2 were set to Ventriculomegaly with cystic kidney disease 219730
Renal ciliopathies v0.1 CEP83 Eleanor Williams gene: CEP83 was added
gene: CEP83 was added to Renal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: CEP83 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP83 were set to 24882706
Phenotypes for gene: CEP83 were set to Nephronophthisis 18 615862
Renal ciliopathies v0.1 CEP41 Eleanor Williams gene: CEP41 was added
gene: CEP41 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: CEP41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP41 were set to 22246503
Phenotypes for gene: CEP41 were set to Joubert syndrome 15
Renal ciliopathies v0.1 CEP290 Eleanor Williams gene: CEP290 was added
gene: CEP290 was added to Renal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: CEP290 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP290 were set to 20690115; 18327255
Phenotypes for gene: CEP290 were set to 610189; Meckel syndrome 4; Senior-Loken syndrome; 611755; Joubert syndrome 5; Joubert syndrome with oculorenal defect; 610188; Senior-Loken syndrome 6; 611134; Meckel syndrome
Renal ciliopathies v0.1 CEP164 Eleanor Williams gene: CEP164 was added
gene: CEP164 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: CEP164 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP164 were set to ciliopathies; Nephronophthisis 15; Senior-Loken syndrome; Nephronophthisis 15, 614845
Renal ciliopathies v0.1 CEP104 Eleanor Williams gene: CEP104 was added
gene: CEP104 was added to Renal ciliopathies. Sources: Other,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: CEP104 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP104 were set to 26477546
Phenotypes for gene: CEP104 were set to Joubert syndrome 25, 616781; Joubert syndrome 25
Renal ciliopathies v0.1 CENPF Eleanor Williams gene: CENPF was added
gene: CENPF was added to Renal ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to 26820108
Phenotypes for gene: CENPF were set to Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Renal ciliopathies v0.1 CC2D2A Eleanor Williams gene: CC2D2A was added
gene: CC2D2A was added to Renal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: CC2D2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CC2D2A were set to Joubert syndrome 9; COACH syndrome; Joubert syndrome with oculorenal defect; Meckel syndrome 6; Meckel syndrome
Renal ciliopathies v0.1 C5orf42 Eleanor Williams gene: C5orf42 was added
gene: C5orf42 was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: C5orf42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C5orf42 were set to 22693042; 25920555; 22425360
Phenotypes for gene: C5orf42 were set to Joubert syndrome; Oral-facial-digital syndrome type VI; Joubert syndrome 17
Renal ciliopathies v0.1 BBS9 Eleanor Williams gene: BBS9 was added
gene: BBS9 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS9 were set to 16380913
Phenotypes for gene: BBS9 were set to Bardet Biedl syndrome 9
Renal ciliopathies v0.1 BBS7 Eleanor Williams gene: BBS7 was added
gene: BBS7 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS7 were set to 12567324
Phenotypes for gene: BBS7 were set to Bardet Biedl syndrome 7
Renal ciliopathies v0.1 BBS5 Eleanor Williams gene: BBS5 was added
gene: BBS5 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS5 were set to 15137946
Phenotypes for gene: BBS5 were set to Bardet Biedl syndrome 5
Renal ciliopathies v0.1 BBS4 Eleanor Williams gene: BBS4 was added
gene: BBS4 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS4 were set to 11381270; 22353939
Phenotypes for gene: BBS4 were set to Bardet Biedl syndrome 4
Renal ciliopathies v0.1 BBS2 Eleanor Williams gene: BBS2 was added
gene: BBS2 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS2 were set to 11285252
Phenotypes for gene: BBS2 were set to Bardet Biedl syndrome 2
Renal ciliopathies v0.1 BBS12 Eleanor Williams gene: BBS12 was added
gene: BBS12 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS12 were set to 17160889
Phenotypes for gene: BBS12 were set to Bardet Biedl syndrome 12
Renal ciliopathies v0.1 BBS10 Eleanor Williams gene: BBS10 was added
gene: BBS10 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS10 were set to 16582908
Phenotypes for gene: BBS10 were set to Bardet Biedl syndrome 10
Renal ciliopathies v0.1 BBS1 Eleanor Williams gene: BBS1 was added
gene: BBS1 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS1 were set to 23143442; 12118255
Phenotypes for gene: BBS1 were set to Bardet Biedl syndrome 13; 268000; Bardet Biedl syndrome 1; Bardet Biedl syndrome 11
Renal ciliopathies v0.1 B9D2 Eleanor Williams gene: B9D2 was added
gene: B9D2 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: B9D2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D2 were set to 21763481 - two affected fetuses form the same family displayed overlapping phenotypes including cystic kidneys, ductal plate malformation, polydactyly, and occipital encephalocele. Homozygous variant identified in this gene, which was not present in the unaffected son. Homozygous variants were not identified in other known Meckel syndrome genes; 26092869 - two further cases with Joubert syndrome reported from two different families
Phenotypes for gene: B9D2 were set to Joubert syndrome; Meckel syndrome 10, 614175; ciliopathies; Meckel syndrome
Renal ciliopathies v0.1 ARMC9 Eleanor Williams gene: ARMC9 was added
gene: ARMC9 was added to Renal ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to 28625504
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30, 617622
Renal ciliopathies v0.1 ARL6 Eleanor Williams gene: ARL6 was added
gene: ARL6 was added to Renal ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: ARL6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6 were set to 15258860; 21282186
Phenotypes for gene: ARL6 were set to {Bardet Biedl syndrome 1, modifier of}; Bardet-Biedl Syndrome; 268000; Bardet Biedl syndrome 3
Renal ciliopathies v0.1 ARL13B Eleanor Williams gene: ARL13B was added
gene: ARL13B was added to Renal ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: ARL13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL13B were set to 18674751; 25138100
Phenotypes for gene: ARL13B were set to Joubert syndrome 8
Renal ciliopathies v0.1 ANKS6 Eleanor Williams gene: ANKS6 was added
gene: ANKS6 was added to Renal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: ANKS6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ANKS6 were set to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, 615382; Nephronophthisis
Renal ciliopathies v0.1 ALMS1 Eleanor Williams gene: ALMS1 was added
gene: ALMS1 was added to Renal ciliopathies. Sources: Expert list,UKGTN,Eligibility statement prior genetic testing,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALMS1 were set to 22773737
Phenotypes for gene: ALMS1 were set to Alstrom Syndrome; Bardet-Biedl Syndrome; 203800; Alstrom syndrome
Renal ciliopathies v0.1 AHI1 Eleanor Williams gene: AHI1 was added
gene: AHI1 was added to Renal ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: AHI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AHI1 were set to Joubert syndrome 3; Joubert syndrome; Joubert syndrome-3.
Renal ciliopathies v0.1 ZNF423 Eleanor Williams gene: ZNF423 was added
gene: ZNF423 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,Expert Review Amber,Radboud University Medical Center, Nijmegen,Orphanet
Mode of inheritance for gene: ZNF423 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ZNF423 were set to 22863007
Phenotypes for gene: ZNF423 were set to Nephronophthisis 14; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect; Joubert syndrome 19; Nephronophthisis 14, 614844
Renal ciliopathies v0.1 IFT27 Eleanor Williams gene: IFT27 was added
gene: IFT27 was added to Renal ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Amber
Mode of inheritance for gene: IFT27 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT27 were set to ?Bardet-Biedl syndrome 19, 615996
Renal ciliopathies v0.1 GLIS2 Eleanor Williams gene: GLIS2 was added
gene: GLIS2 was added to Renal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Expert Review Amber,Radboud University Medical Center, Nijmegen,Orphanet,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: GLIS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLIS2 were set to 26374130; 23559409; 17618285; 18227149
Phenotypes for gene: GLIS2 were set to Nephronophthisis; NPHP; Nephronophthisis 7, 611498
Ophthalmological ciliopathies v0.3 ZNF423 Ivone Leong gene: ZNF423 was added
gene: ZNF423 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,Expert Review Amber,Radboud University Medical Center, Nijmegen,Orphanet
Mode of inheritance for gene: ZNF423 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ZNF423 were set to 22863007
Phenotypes for gene: ZNF423 were set to Nephronophthisis 14; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect; Joubert syndrome 19; Nephronophthisis 14, 614844
Ophthalmological ciliopathies v0.3 POC1B Ivone Leong gene: POC1B was added
gene: POC1B was added to Ophthalmological ciliopathies. Sources: UKGTN,Expert list,Expert Review Amber
Mode of inheritance for gene: POC1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1B were set to 29377742; 25044745; 29220607; 25018096; 24945461
Phenotypes for gene: POC1B were set to Senior-Loken Syndrome 24 gene panel; Cone-rod dystrophy 20 615973; Joubert Syndrome; AUTOSOMAL-RECESSIVE CONE-ROD DYSTROPHY
Ophthalmological ciliopathies v0.3 IFT27 Ivone Leong gene: IFT27 was added
gene: IFT27 was added to Ophthalmological ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Amber
Mode of inheritance for gene: IFT27 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT27 were set to ?Bardet-Biedl syndrome 19, 615996
Skeletal ciliopathies v0.0 Eleanor Williams Added Panel Skeletal ciliopathies
Set panel types to: GMS Rare Disease Virtual
Renal ciliopathies v0.0 Eleanor Williams Added Panel Renal ciliopathies
Set panel types to: GMS Rare Disease Virtual
Neurological ciliopathies v0.0 Louise Daugherty Added Panel Neurological ciliopathies
Set panel types to: GMS Rare Disease Virtual
Differences in sex development v1.36 ZFPM2 Ivone Leong Classified gene: ZFPM2 as Amber List (moderate evidence)
Differences in sex development v1.36 ZFPM2 Ivone Leong Added comment: Comment on list classification: Demoted from green to amber based on the evidence provided by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust).
Differences in sex development v1.36 ZFPM2 Ivone Leong Gene: zfpm2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.147 ALPL Rebecca Foulger Added comment: Comment on publications: ALPL is called by its alias TNSALP in many publications.
Early onset or syndromic epilepsy v1.147 ALPL Rebecca Foulger Publications for gene: ALPL were set to
Mitochondrial disorders v1.404 IARS2 Sarah Leigh Classified gene: IARS2 as Green List (high evidence)
Mitochondrial disorders v1.404 IARS2 Sarah Leigh Added comment: Comment on list classification: Based on additional variants in publications reported by Zornitza Stark (Australian Genomics).
Mitochondrial disorders v1.404 IARS2 Sarah Leigh Gene: iars2 has been classified as Green List (High Evidence).
Intellectual disability v2.949 HK1 Ivone Leong Classified gene: HK1 as Green List (high evidence)
Intellectual disability v2.949 HK1 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There are sufficient cases for this gene to be promote to green status. Variants on the 5' end of the gene have been associated with neuropathy, hereditary motor and sensory, Russe type.
Intellectual disability v2.949 HK1 Ivone Leong Gene: hk1 has been classified as Green List (High Evidence).
Intellectual disability v2.948 HK1 Ivone Leong Added comment: Comment on mode of pathogenicity: A gain of function effect is presumed to cause disease.
Intellectual disability v2.948 HK1 Ivone Leong Mode of pathogenicity for gene: HK1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v1.146 WDR62 Rebecca Foulger Publications for gene: WDR62 were set to 21834044; 20890278; 20729831
Intellectual disability v2.947 HK1 Ivone Leong Phenotypes for gene: HK1 were changed from Hemolytic anemia due to hexokinase deficiency, 235700; Neuropathy, hereditary motor and sensory, Russe type, 605285 to Hemolytic anemia due to hexokinase deficiency, 235700; Neuropathy, hereditary motor and sensory, Russe type, 605285; Abnormal muscle tone; Global developmental delay; Intellectual disability; Visual impairment; Neurological speech impairment; Ataxia
Intellectual disability v2.946 HK1 Ivone Leong Publications for gene: HK1 were set to
Intellectual disability v2.945 HK1 Ivone Leong Tag missense tag was added to gene: HK1.
Intellectual disability v2.945 NDUFAF5 Ivone Leong Classified gene: NDUFAF5 as Amber List (moderate evidence)
Intellectual disability v2.945 NDUFAF5 Ivone Leong Added comment: Comment on list classification: Promoted from red to amber. This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. After discussion with the Genomics England Clinical Team it was decided that there is currently not enough evidence to promote this gene to green. The clinical presentations reported in the papers are not classical for an ID cohort (except perhaps patient 1 in the Ashkenzi Jewish families). Therefore, this gene has been promoted to amber until further evidence emerges.
Intellectual disability v2.945 NDUFAF5 Ivone Leong Gene: ndufaf5 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.145 WDR45B Rebecca Foulger Added comment: Comment on phenotypes: Now (July 9th 2019) associated with a disorder in OMIM (617977).
Early onset or syndromic epilepsy v1.145 WDR45B Rebecca Foulger Phenotypes for gene: WDR45B were changed from profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations to Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977; profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations
Intellectual disability v2.944 SMARCD1 Ivone Leong Classified gene: SMARCD1 as Green List (high evidence)
Intellectual disability v2.944 SMARCD1 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. SMARCD1 is not associated with any phenotype in OMIM or Gene2Phenotype. After consulting with the Genomics England Clinical Team and based on the submitted expert review, it was decided that there is enough evidence to promote this gene to green status.
Intellectual disability v2.944 SMARCD1 Ivone Leong Gene: smarcd1 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v1.2 Ivone Leong Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Mitochondrial disorders v1.403 GATM Sarah Leigh Classified gene: GATM as Red List (low evidence)
Mitochondrial disorders v1.403 GATM Sarah Leigh Added comment: Comment on list classification: Additional phenocopy gene identified, phenotype is not particularly relevant
Mitochondrial disorders v1.403 GATM Sarah Leigh Gene: gatm has been classified as Red List (Low Evidence).
Proteinuric renal disease v1.221 PDSS2 Eleanor Williams changed review comment from: Comment on list classification: 4 cases plus a mouse knock out model.; to: Comment on list classification: Upgraded from red to green. 4 cases plus a mouse knock out model.
Intellectual disability v2.943 SMARCD1 Ivone Leong Mode of inheritance for gene: SMARCD1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v2.942 SMARCD1 Ivone Leong Phenotypes for gene: SMARCD1 were changed from to Generalized hypotonia; Feeding difficulties; Global developmental delay; Intellectual disability; Abnormality of the hand; Abnormality of the foot
Proteinuric renal disease v1.221 PDSS2 Eleanor Williams Publications for gene: PDSS2 were set to 23926186
Proteinuric renal disease v1.220 PDSS2 Eleanor Williams Mode of inheritance for gene: PDSS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.219 PDSS2 Eleanor Williams Classified gene: PDSS2 as Green List (high evidence)
Proteinuric renal disease v1.219 PDSS2 Eleanor Williams Added comment: Comment on list classification: 4 cases plus a mouse knock out model.
Proteinuric renal disease v1.219 PDSS2 Eleanor Williams Gene: pdss2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.218 PDSS2 Eleanor Williams edited their review of gene: PDSS2: Added comment: The gene is associated with Coenzyme Q10 deficiency, primary, 3 (#614652) in OMIM and COENZYME Q10 DEFICIENCY, PRIMARY, 3 (confirmed) in Gene2Phenotype.

PMID: 29032433 - Iványi et al 2018 - 1 case - male child of healthy, nonconsanguineous Caucasian parents. At 7 months of age he had general edema, muscle hypotonia, mild inspiratory stridor, and global developmental delay. He did not react to auditory stimuli, and they detected no tracking and focusing eye movements. Urinalysis revealed proteinuria. A heterozygous missense mutation in the PDSS2 gene in exon 3 was found (c.485A > G, p.His162Arg) (maternally inherited) along with a heterozygous 2923-bp deletion that affected a part of exon 8 in the PDSS2 gene. The paternal allele is the NM_020381.3:c.1042_1148-2816del, which causes a 107-base long deletion of exon 8. Despite high-dose CoQ10 treatment he died at 8 months of age.

PMID: 25349199 - Sadowski et al 2015 - 2 cases with homozygous missense changes in PDSS2 in patients with Steroid-resistant nephrotic syndrome. They performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with Steroid-resistant nephrotic syndrome (SRNS) and then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. 2 families were molecularly diagnosed with a causative variant in PDSS2 by multiplex PCR (c.1145C>T,p.Ser382Leu and c.1151C>A, p.Ala384Asp).

PMID: 23926186 - Gasser et al 2013 - genotyped 377 patients with primary Focal segmental glomerulosclerosis (FSGS) or collapsing glomerulopathy, together with 900 controls, for 9 single-nucleotide polymorphisms in the PDSS2 gene in a case-control study. The nine selected SNPs were distributed at approximately equal distances across the PDSS2 gene. All the SNPs that were genotyped occurred within noncoding regions of the gene. They demonstrated that homozygous genotypes for variant alleles for the PDSS2 gene were more common in FSGS patients than controls and that a single haplotype containing three of these SNPs was more common in European American, but not African American, FSGS patients, suggesting that PDSS2 may be an FSGS susceptibility gene.

PMID:17186472 - Lopez et al 2006 - 1 family with child who presented with neonatal pneumonia and hypotonia, developed refractory left-sided seizures with secondary generalization, and became progressively floppy. At age 7 mo, severe episodic vomiting prompted duodenal tube feeding, and was diagnosed with nephrotic syndrome due to low serum albumin and massive proteinuria. They found two nonsynonymous nucleotide changes in PDSS2, each inherited from one parent. Functional tests on cultured patient fibroblast indicate that endogenous levels of decaprenyl diphosphate are reduced.

Mouse model:
PMID: 18437205 - Peng et al 2008 - Kidney disease in mice with missense Pdss2(kd/kd) genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd) mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP) knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes.

Summary:
4 cases of children with nephrotic syndrome and homozygous or compound heterozygous variants in PDSS2. In two cases the variants are reported to segregate with the disease in the family. Additional evidence from a case control study that PDSS2 is a FSGS susceptibility gene and from a mouse Pdss2 knockout model.; Changed publications: PMID: 23926186
Intellectual disability v2.941 CTBP1 Rebecca Foulger Phenotypes for gene: CTBP1 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Ataxia; Abnormality of dental enamel to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, 617915
Intellectual disability v2.940 TRPM3 Rebecca Foulger Classified gene: TRPM3 as Amber List (moderate evidence)
Intellectual disability v2.940 TRPM3 Rebecca Foulger Added comment: Comment on list classification: TRPM3 was added to the panel and rated Green by Konstantinos Varvagiannis based on PMID:31278393 (Dyment et al 2019). Although 8 probands were reported, 1 proband carries a VUS and an additional splice variant in DDB1. Therefore only variant is pathogenic, and this is missense, and de novo in all cases. The authors also note that heterozygous LOF variants in TRPM3 are observed in the general population. Not yet associated with a disorder in Gene2Phenotype or OMIM. Therefore have rated Amber and added 'watchlist' tag awaiting further cases or additional functional studies.
Intellectual disability v2.940 TRPM3 Rebecca Foulger Gene: trpm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.939 TRPM3 Rebecca Foulger Tag missense tag was added to gene: TRPM3.
Tag watchlist tag was added to gene: TRPM3.
Intellectual disability v2.939 TRPM3 Rebecca Foulger Publications for gene: TRPM3 were set to doi.org/10.1038/s41431-019-0462-x
Intellectual disability v2.938 TRPM3 Rebecca Foulger commented on gene: TRPM3
Early onset or syndromic epilepsy v1.144 TRPM3 Rebecca Foulger Classified gene: TRPM3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.144 TRPM3 Rebecca Foulger Added comment: Comment on list classification: TRPM3 was added to the panel and rated Green by Konstantinos Varvagiannis based on PMID:31278393 (Dyment et al 2019). Although 8 probands were reported, 1 proband carries a VUS and an additional splice variant in DDB1. Therefore only variant is pathogenic, and this is missense, and de novo in all cases. The authors also note that heterozygous LOF variants in TRPM3 are observed in the general population. Not yet associated with a disorder in Gene2Phenotype or OMIM. Therefore have rated Amber and added 'watchlist' tag awaiting further cases or additional functional studies.
Early onset or syndromic epilepsy v1.144 TRPM3 Rebecca Foulger Gene: trpm3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.143 TRPM3 Rebecca Foulger commented on gene: TRPM3
Early onset or syndromic epilepsy v1.143 TRPM3 Rebecca Foulger Tag watchlist tag was added to gene: TRPM3.
Early onset or syndromic epilepsy v1.143 TRPM3 Rebecca Foulger Tag missense tag was added to gene: TRPM3.
Early onset or syndromic epilepsy v1.143 TRPM3 Rebecca Foulger Publications for gene: TRPM3 were set to doi.org/10.1038/s41431-019-0462-x
Early onset or syndromic epilepsy v1.142 CLCN6 Sarah Leigh Added comment: Comment on publications: PMID 29667327 - one case with seizures, no other work up

PMID 26658788 - reference to rare traits and BP control

PMID 25794116 - three families with variants and a history of seizures. However one person with a reported phenotype of seizures was variant negative and the functional work does not look compelling
Early onset or syndromic epilepsy v1.142 CLCN6 Sarah Leigh Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116
Early onset or syndromic epilepsy v1.141 CLCN6 Sarah Leigh Classified gene: CLCN6 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.141 CLCN6 Sarah Leigh Gene: clcn6 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.140 CLCN6 Sarah Leigh gene: CLCN6 was added
gene: CLCN6 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CLCN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116
Review for gene: CLCN6 was set to AMBER
Added comment: Sources: Literature
Neuronal ceroid lipofuscinosis v0.6 CLCN6 Sarah Leigh Publications for gene: CLCN6 were set to
Severe hypertriglyceridaemia v1.10 CREB3L3 Sarah Leigh Classified gene: CREB3L3 as Green List (high evidence)
Severe hypertriglyceridaemia v1.10 CREB3L3 Sarah Leigh Gene: creb3l3 has been classified as Green List (High Evidence).
Severe hypertriglyceridaemia v1.9 CREB3L3 Sarah Leigh gene: CREB3L3 was added
gene: CREB3L3 was added to Severe hypertriglyceridaemia. Sources: Literature
Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CREB3L3 were set to 29954705; 21666694; 26427795; 22135386
Phenotypes for gene: CREB3L3 were set to monogenic dominant hypertriglyceridemia associated with CREB3L3
Review for gene: CREB3L3 was set to GREEN
Added comment: Not associated with phenotype in OMIM (last updated in 02/06/2015) or in Gen2Phen. At least three terminating variants have been identified in unrelated cases, together with supportive functional studies
Sources: Literature
Adult onset neurodegenerative disorder v1.63 CTSF Louise Daugherty Publications for gene: CTSF were set to 23297359: 25274848
Adult onset neurodegenerative disorder v1.62 CTSF Louise Daugherty Classified gene: CTSF as Green List (high evidence)
Adult onset neurodegenerative disorder v1.62 CTSF Louise Daugherty Added comment: Comment on list classification: New gene added from curation of Undiagnosed metabolic disorders panel and recommended by Genomics England clinical team to add to the Neurodegenerative disorders - adult onset panel. This is reported with onset in adulthood (youngest 20 yrs, oldest 35 yrs) with neurological features and cognitive decline.
Adult onset neurodegenerative disorder v1.62 CTSF Louise Daugherty Gene: ctsf has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v1.61 CTSF Sarah Leigh changed review comment from: Associated with phenotype in OMIM (last updated 02/06/2015) or in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, together with supportive functional studies.
Sources: Literature; to: Associated with phenotype in OMIM but not in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, together with supportive functional studies.
Sources: Literature
Hereditary neuropathy v1.333 TTR Louise Daugherty Phenotypes for gene: TTR were changed from Cardiomyopathy to Amyloidosis, hereditary, transthyretin-related, 105210; FAP; Cardiomyopathy
Hereditary neuropathy v1.332 TTR Louise Daugherty Publications for gene: TTR were set to
Adult onset neurodegenerative disorder v1.61 CTSF Sarah Leigh Phenotypes for gene: CTSF were changed from Type B Kufs disease to Ceroid lipofuscinosis, neuronal, 13, Kufs type 615362
Proteinuric renal disease v1.218 LCAT Eleanor Williams Classified gene: LCAT as Amber List (moderate evidence)
Proteinuric renal disease v1.218 LCAT Eleanor Williams Added comment: Comment on list classification: Changing the rating from green to amber until a review of the degree of proteinuria in patients with Norum disease has been carried out.
Proteinuric renal disease v1.218 LCAT Eleanor Williams Gene: lcat has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v1.217 AMN Eleanor Williams Classified gene: AMN as Amber List (moderate evidence)
Proteinuric renal disease v1.217 AMN Eleanor Williams Added comment: Comment on list classification: Changing rating from green to amber until a review of the degree of proteinuria in patients with Imerslund-Grasbeck syndrome has been done.
Proteinuric renal disease v1.217 AMN Eleanor Williams Gene: amn has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v1.60 CTSF Sarah Leigh changed review comment from: Not associated with phenotype in OMIM (last updated 02/06/2015) or in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, together with supportive functional studies.
Sources: Literature; to: Associated with phenotype in OMIM (last updated 02/06/2015) or in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, together with supportive functional studies.
Sources: Literature
Adult onset neurodegenerative disorder v1.60 CTSF Sarah Leigh changed review comment from: Not associated with phenotype in OMIM (last updated 02/06/2015) or in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, toghether with supportive functional studies.
Sources: Literature; to: Not associated with phenotype in OMIM (last updated 02/06/2015) or in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, together with supportive functional studies.
Sources: Literature
Adult onset neurodegenerative disorder v1.60 CTSF Sarah Leigh gene: CTSF was added
gene: CTSF was added to Neurodegenerative disorders - adult onset. Sources: Literature
Mode of inheritance for gene: CTSF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSF were set to 23297359: 25274848
Phenotypes for gene: CTSF were set to Type B Kufs disease
Review for gene: CTSF was set to GREEN
Added comment: Not associated with phenotype in OMIM (last updated 02/06/2015) or in Gen2Phen. This gene was reported in the GMS Neuronal ceroid lipofuscinosis panel as a green gene. At least six variants have been reported in patients with neurological features and cognitive decline, toghether with supportive functional studies.
Sources: Literature
Primary lymphoedema v1.82 TTR Ellen McDonagh Publications for gene: TTR were set to
Primary lymphoedema v1.81 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Primary lymphoedema v1.81 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Hereditary neuropathy v1.331 TTR Ellen McDonagh edited their review of gene: TTR: Added comment: The 'treatable' tag has been added due to new therapies available that target this gene. Inotersen is an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), developed and approved by NICE for the treatment of hereditary transthyretin amyloidosis (hATTR) (PMID: 30120737, https://www.nice.org.uk/guidance/hst9/chapter/1-Recommendations). Patisiran is a small interfering RNA (siRNA) molecule that targets the transthyretin gene (TTR) messenger mRNA (mRNA), to suppress both mutant and wild-type amyloid transthyretin (ATTR) protein production. This drug has been approved by NHSE for treatment of transthyretin-mediated amyloidosis (https://www.bbc.co.uk/news/health-48907976).; Changed publications: 30878017, 31131842, 31118583, 31111153, 30120737; Changed phenotypes: Amyloidosis, hereditary, transthyretin-related 105210
Hereditary neuropathy v1.331 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Paroxysmal central nervous system disorders v0.20 TTR Ellen McDonagh Publications for gene: TTR were set to 12771253; The Metabolic and Molecular Bases of Inherited Disease. Vol. IV. 8th ed.Benson, M. D. Amyloidosis. In: Scriver, C. R et al.: New York: McGraw-Hill . 2001.; 25069833; 19365058; 28678039; 26800456; 8309582; 14640030; 16433699; 3011930
Paroxysmal central nervous system disorders v0.19 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Paroxysmal central nervous system disorders v0.19 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Pain syndromes v1.6 TTR Ellen McDonagh Publications for gene: TTR were set to 3011930; 14640030; 28678039; 26800456; 25069833; 12771253; 19365058; 16433699; 8309582; The Metabolic and Molecular Bases of Inherited Disease. Vol. IV. 8th ed.Benson, M. D. Amyloidosis. In: Scriver, C. R et al.: New York: McGraw-Hill . 2001.
Pain syndromes v1.5 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Pain syndromes v1.5 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Hypertrophic cardiomyopathy v1.56 TTR Ellen McDonagh Publications for gene: TTR were set to 28475415; 16115295; 16194874; 26537620; 1626570; 1570831
Hypertrophic cardiomyopathy v1.55 TTR Ellen McDonagh edited their review of gene: TTR: Added comment: The 'treatable' tag has been added due to new therapies available that target this gene. Inotersen is an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), developed and approved by NICE for the treatment of hereditary transthyretin amyloidosis (hATTR) (PMID: 30120737, https://www.nice.org.uk/guidance/hst9/chapter/1-Recommendations). Patisiran is a small interfering RNA (siRNA) molecule that targets the transthyretin gene (TTR) messenger mRNA (mRNA), to suppress both mutant and wild-type amyloid transthyretin (ATTR) protein production. This drug has been approved by NHSE for treatment of transthyretin-mediated amyloidosis (https://www.bbc.co.uk/news/health-48907976).; Changed publications: 30878017, 31131842, 31118583, 31111153, 30120737
Hypertrophic cardiomyopathy v1.55 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Hereditary systemic amyloidosis v0.7 TTR Ellen McDonagh Phenotypes for gene: TTR were changed from 105210 to Amyloidosis, hereditary, transthyretin-related 105210
Hydrocephalus v1.31 TTR Ellen McDonagh Publications for gene: TTR were set to
Hydrocephalus v1.30 TTR Ellen McDonagh edited their review of gene: TTR: Changed publications: 30878017, 31131842, 31118583, 31111153, 30120737; Changed phenotypes: Amyloidosis, hereditary, transthyretin-related 105210
Hydrocephalus v1.30 TTR Ellen McDonagh commented on gene: TTR
Hydrocephalus v1.30 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Early onset or syndromic epilepsy v1.139 NPRL2 Rebecca Foulger commented on gene: NPRL2
Early onset or syndromic epilepsy v1.139 NPRL2 Rebecca Foulger Phenotypes for gene: NPRL2 were changed from Epilepsy, familial focal, with variable foci 2 617116 to Epilepsy, familial focal, with variable foci 2, 617116
Early onset or syndromic epilepsy v1.138 NPRL2 Rebecca Foulger Publications for gene: NPRL2 were set to 26505888; 27173016
Early onset or syndromic epilepsy v1.137 KPTN Rebecca Foulger Phenotypes for gene: KPTN were changed from Mental retardation, autosomal recessive 41615637 to Mental retardation, autosomal recessive 4,1615637; seizures
Early onset or syndromic epilepsy v1.136 KPTN Rebecca Foulger Classified gene: KPTN as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.136 KPTN Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber following evaluation of Green review by Zornitza. No further cases of KPTN variants associated with epilepsy/seizures are reported in the literature since PMID:24239382 (Baple et al., 2014: Founder effect in Amish community) and PMID:25847626 (Pajualu et al. 2015, 2 Estonian siblings with seizures in the brother). Although the association with ID is clearer, more epilepsy cases are required for a diagnostic-grade rating.
Early onset or syndromic epilepsy v1.136 KPTN Rebecca Foulger Gene: kptn has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.135 CYP27A1 Rebecca Foulger Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis 213700 to Cerebrotendinous xanthomatosis, 213700; seizures; photosensitive epilepsy
Early onset or syndromic epilepsy v1.134 CYP27A1 Rebecca Foulger Publications for gene: CYP27A1 were set to 18227423
Early onset or syndromic epilepsy v1.133 CYP27A1 Rebecca Foulger Classified gene: CYP27A1 as Green List (high evidence)
Early onset or syndromic epilepsy v1.133 CYP27A1 Rebecca Foulger Added comment: Comment on list classification: Upgraded rating from Red to Green based on external review by Philip Dawson. Although seizures are not a consistent feature of CTX patients, there are plenty of cases in the literature of seizures reported in CTX cohorts and individual cases (e.g. PMIDs 29484516 and 22336472) to support inclusion on this panel.
Early onset or syndromic epilepsy v1.133 CYP27A1 Rebecca Foulger Gene: cyp27a1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.132 CYP27A1 Rebecca Foulger changed review comment from: PMID:29484516. Wong et al 2018 evaluated 5 cases of cerebrotendinous xanthomatosis (CTX) patients.
CTX is an autosomal recessive condition caused by variants in CYP27A1. Seizures reported in 1/5 cases at 24 years old.; to: PMID:29484516. Wong et al 2018 evaluated 5 cases of cerebrotendinous xanthomatosis (CTX) patients. CTX is an autosomal recessive condition caused by variants in CYP27A1. Seizures reported in 1/5 cases at 24 years old. They also analysed 194 cases from the literature and reported seizures in 37/194 cases (19%).
Early onset or syndromic epilepsy v1.132 CYP27A1 Rebecca Foulger commented on gene: CYP27A1: PMID:22336472. Koyama et al. 2012. An 18 year old Japanese female with a history of epileptic seizures amongst her phenotypes. She had compound heterozygous variants in CYP27A1: maternally-inherited V413D and paternally-inherited R474W. The variants were not present in Japanese controls.
Early onset or syndromic epilepsy v1.132 CYP27A1 Rebecca Foulger commented on gene: CYP27A1: PMID:24442603. Mignarri et al 2014. In their CTX cohort of 55 patients, 18 were reported with epilepsy (33%). They report 14/54 (26%) and 8/25 (32%) of epilepsy cases in previous cohorts.
Early onset or syndromic epilepsy v1.132 CYP27A1 Rebecca Foulger commented on gene: CYP27A1: PMID:29484516. Wong et al 2018 evaluated 5 cases of cerebrotendinous xanthomatosis (CTX) patients.
CTX is an autosomal recessive condition caused by variants in CYP27A1. Seizures reported in 1/5 cases at 24 years old.
Early onset or syndromic epilepsy v1.132 CYP27A1 Rebecca Foulger commented on gene: CYP27A1
Adult onset neurodegenerative disorder v1.59 ISCA-37404-Loss Louise Daugherty changed review comment from: Red rating for CNV region submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.; to: Red rating for CNV region submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 C9orf72_GGGGCC Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 C9orf72_GGGGCC Louise Daugherty commented on STR: C9orf72_GGGGCC: Green rating inferred from review comment on the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 ATXN7_CAG Louise Daugherty commented on STR: ATXN7_CAG: Green rating inferred from review comment of the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 ATXN3_CAG Louise Daugherty commented on STR: ATXN3_CAG: Green rating inferred from review comment of the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 ATXN3_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 ATXN2_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 ATXN2_CAG Louise Daugherty commented on STR: ATXN2_CAG: Green rating inferred from review comment of the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 ATXN1_CAG Louise Daugherty commented on STR: ATXN1_CAG: Green rating inferred from review comment of the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 ATXN1_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group. ; to: Green rating for STR submitted on behalf of James Polke, also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 ATXN10_ATTCT Louise Daugherty commented on STR: ATXN10_ATTCT: Green rating inferred from review comment of the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 ATXN10_ATTCT Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 ATN1_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group. ; to: Green rating for STR submitted on behalf of James Polke, also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.59 ATN1_CAG Louise Daugherty commented on STR: ATN1_CAG: Green rating inferred from review comment on the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.
Adult onset neurodegenerative disorder v1.59 PPP2R2B_CAG Louise Daugherty Source NHS GMS was added to STR: PPP2R2B_CAG.
Adult onset neurodegenerative disorder v1.59 NOP56_GGCCTG Louise Daugherty Source NHS GMS was added to STR: NOP56_GGCCTG.
Adult onset neurodegenerative disorder v1.59 JPH3_CTG Louise Daugherty Source NHS GMS was added to STR: JPH3_CTG.
Adult onset neurodegenerative disorder v1.59 HTT_CAG Louise Daugherty Source NHS GMS was added to STR: HTT_CAG.
Adult onset neurodegenerative disorder v1.59 C9orf72_GGGGCC Louise Daugherty Source NHS GMS was added to STR: C9orf72_GGGGCC.
Adult onset neurodegenerative disorder v1.59 ATXN7_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN7_CAG.
Adult onset neurodegenerative disorder v1.59 ATXN3_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN3_CAG.
Adult onset neurodegenerative disorder v1.59 ATXN2_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN2_CAG.
Adult onset neurodegenerative disorder v1.59 ATXN1_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN1_CAG.
Adult onset neurodegenerative disorder v1.59 ATXN10_ATTCT Louise Daugherty Source NHS GMS was added to STR: ATXN10_ATTCT.
Adult onset neurodegenerative disorder v1.59 ATN1_CAG Louise Daugherty Source NHS GMS was added to STR: ATN1_CAG.
Adult onset neurodegenerative disorder v1.59 AR_CAG Louise Daugherty Source NHS GMS was added to STR: AR_CAG.
Adult onset neurodegenerative disorder v1.58 C9orf72_GGGGCC Louise Daugherty Source South West GLH was added to STR: C9orf72_GGGGCC.
Adult onset neurodegenerative disorder v1.58 ATXN7_CAG Louise Daugherty Source South West GLH was added to STR: ATXN7_CAG.
Adult onset neurodegenerative disorder v1.58 ATXN3_CAG Louise Daugherty Source South West GLH was added to STR: ATXN3_CAG.
Adult onset neurodegenerative disorder v1.58 ATXN2_CAG Louise Daugherty Source South West GLH was added to STR: ATXN2_CAG.
Adult onset neurodegenerative disorder v1.58 ATXN1_CAG Louise Daugherty Source South West GLH was added to STR: ATXN1_CAG.
Adult onset neurodegenerative disorder v1.58 ATXN10_ATTCT Louise Daugherty Source South West GLH was added to STR: ATXN10_ATTCT.
Adult onset neurodegenerative disorder v1.58 ATN1_CAG Louise Daugherty Source South West GLH was added to STR: ATN1_CAG.
Adult onset neurodegenerative disorder v1.57 PPP2R2B_CAG Louise Daugherty Source London North GLH was added to STR: PPP2R2B_CAG.
Adult onset neurodegenerative disorder v1.57 NOP56_GGCCTG Louise Daugherty Source London North GLH was added to STR: NOP56_GGCCTG.
Adult onset neurodegenerative disorder v1.57 JPH3_CTG Louise Daugherty Source London North GLH was added to STR: JPH3_CTG.
Adult onset neurodegenerative disorder v1.57 HTT_CAG Louise Daugherty Source London North GLH was added to STR: HTT_CAG.
Adult onset neurodegenerative disorder v1.57 C9orf72_GGGGCC Louise Daugherty Source London North GLH was added to STR: C9orf72_GGGGCC.
Adult onset neurodegenerative disorder v1.57 ATXN7_CAG Louise Daugherty Source London North GLH was added to STR: ATXN7_CAG.
Adult onset neurodegenerative disorder v1.57 ATXN3_CAG Louise Daugherty Source London North GLH was added to STR: ATXN3_CAG.
Adult onset neurodegenerative disorder v1.57 ATXN2_CAG Louise Daugherty Source London North GLH was added to STR: ATXN2_CAG.
Adult onset neurodegenerative disorder v1.57 ATXN1_CAG Louise Daugherty Source London North GLH was added to STR: ATXN1_CAG.
Adult onset neurodegenerative disorder v1.57 ATXN10_ATTCT Louise Daugherty Source London North GLH was added to STR: ATXN10_ATTCT.
Adult onset neurodegenerative disorder v1.57 ATN1_CAG Louise Daugherty Source London North GLH was added to STR: ATN1_CAG.
Publications for STR: ATN1_CAG were changed from 20301664; 8136840; 20301664; 8136840; 8136826; 7614090 to 20301664; 8136826; 8136840; 7614090
Adult onset neurodegenerative disorder v1.57 AR_CAG Louise Daugherty Source London North GLH was added to STR: AR_CAG.
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger changed review comment from: Comment on list classification: Updated rating of TTN on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Lucy Raymond left on the 'DDG2P' panel. TTN was original Red on the DDG2P panel based on a 'possible' DDG2P Disease confidence for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' (MOI: biallelic). TTN was upgraded to Green on the 'Fetal anomalies' panel following clinical review, and there are sufficient cases from PMIDs 29691892, 28040389, 29575618) to support inclusion on this paediatric panel.; to: Comment on list classification: Updated rating of TTN on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Lucy Raymond left on the 'DDG2P' panel. TTN was original Red on the DDG2P panel based on a 'possible' DDG2P Disease confidence for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' (MOI: biallelic). TTN was upgraded to Green on the 'Fetal anomalies' panel following clinical review, and there are sufficient cases from PMIDs 29691892, 28040389, 29575618 to support inclusion on this paediatric panel.
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger Classified gene: TTN as Green List (high evidence)
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger Added comment: Comment on list classification: Updated rating of TTN on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Lucy Raymond left on the 'DDG2P' panel. TTN was original Red on the DDG2P panel based on a 'possible' DDG2P Disease confidence for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' (MOI: biallelic). TTN was upgraded to Green on the 'Fetal anomalies' panel following clinical review, and there are sufficient cases from PMIDs 29691892, 28040389, 29575618) to support inclusion on this paediatric panel.
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger Gene: ttn has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.15 ASCC1 Rebecca Foulger Classified gene: ASCC1 as Green List (high evidence)
Paediatric disorders - additional genes v0.15 ASCC1 Rebecca Foulger Added comment: Comment on list classification: Updated rating of ASCC1 on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Julia Baptista left on the 'DDG2P' panel and the 'Fetal anomalies' panel. ASCC1 was originally Red on the DDG2P panel based on a Gene2Phenotype Disease confidence rating of 'possible' for: Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures (MOI: biallelic). There are sufficient cases to support inclusion as a Green paediatric gene as per Julia Baptista's review. ASCC1 is already Green on the Fetal anomalies panel, and the Arthrogryposis panel.
Paediatric disorders - additional genes v0.15 ASCC1 Rebecca Foulger Gene: ascc1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.14 ASCC1 Rebecca Foulger Phenotypes for gene: ASCC1 were changed from Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures to Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures; spinal muscular atrophy; arthrogryposis; fetal akinesia; hypotonia; contractures
Paediatric disorders - additional genes v0.13 ASCC1 Rebecca Foulger Publications for gene: ASCC1 were set to 26924529
Hereditary systemic amyloidosis v0.6 TTR Ellen McDonagh Publications for gene: TTR were set to 30328212; 14640030
Hereditary systemic amyloidosis v0.5 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Paediatric disorders - additional genes v0.12 ASCC1 Rebecca Foulger commented on gene: ASCC1: My review from 18th Nov 2018 was imported from the DDG2P panel.
Hereditary systemic amyloidosis v0.5 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Familial dysautonomia v1.7 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Paediatric disorders - additional genes v0.12 TTN Rebecca Foulger commented on gene: TTN: My reviews from 19th Nov 2018 and 18th April 2019 were imported from the DDG2P panel.
Familial dysautonomia v1.7 TTR Ellen McDonagh Publications for gene: TTR were set to 12978172
Paediatric disorders - additional genes v0.12 TTN Rebecca Foulger commented on gene: TTN: ASCC1 was added to this 'Paediatric disorders - additional genes panel' to allow curation of the review by Lucy Raymond left on the DDG2P panel (Review left April 2019).
Familial dysautonomia v1.6 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Paediatric disorders - additional genes v0.12 ASCC1 Rebecca Foulger commented on gene: ASCC1: ASCC1 was added to this 'Paediatric disorders - additional genes panel' to allow curation of the review by Julia Baptista left on the DDG2P panel (Review left March 2019).
Periodic fever syndromes v1.11 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Periodic fever syndromes v1.11 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Paediatric disorders - additional genes v0.11 TTN Rebecca Foulger gene: TTN was added
gene: TTN was added to Paediatric disorders - additional genes. Sources: Expert Review Red
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 29575618; 17444505; 29691892; 28040389
Phenotypes for gene: TTN were set to CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY
Paediatric disorders - additional genes v0.11 ASCC1 Rebecca Foulger gene: ASCC1 was added
gene: ASCC1 was added to Paediatric disorders - additional genes. Sources: Expert Review Red
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to 26924529
Phenotypes for gene: ASCC1 were set to Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures
Periodic fever syndromes v1.11 TTR Ellen McDonagh Publications for gene: TTR were set to 20301373; 11385707
Familial hypercholesterolaemia v1.25 CYP27A1 Sarah Leigh Classified gene: CYP27A1 as Green List (high evidence)
Familial hypercholesterolaemia v1.25 CYP27A1 Sarah Leigh Added comment: Comment on list classification: This gene is rated as green as Tendon xanthomas are a feature of Cerebrotendinous xanthomatosis, 213700, which could lead to patients being investigated for FH.
Familial hypercholesterolaemia v1.25 CYP27A1 Sarah Leigh Gene: cyp27a1 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.117 CLIC5 Eleanor Williams Classified gene: CLIC5 as Amber List (moderate evidence)
Monogenic hearing loss v1.117 CLIC5 Eleanor Williams Added comment: Comment on list classification: Downgrading the rating from green to amber as upon review there was only 1 case, plus some functional data from mouse.
Monogenic hearing loss v1.117 CLIC5 Eleanor Williams Gene: clic5 has been classified as Amber List (Moderate Evidence).
Familial chylomicronaemia syndrome (FCS) v0.8 LIPI Sarah Leigh changed review comment from: Comment on list classification: The gene / disease association has been recently been revoked on OMIM as the reclassified variant (rs11909217) is present in 1,382 of 282,752 alleles and in 8 homozygotes in the gnomAD database (Personal communication to OMIM by Ada Hamosh June 25, 2019).; to: Comment on list classification: The gene / disease association has been recently been reclassified on OMIM as the variant (rs11909217) is present in 1,382 of 282,752 alleles and in 8 homozygotes in the gnomAD database (Personal communication to OMIM by Ada Hamosh June 25, 2019).
Familial chylomicronaemia syndrome (FCS) v0.8 LIPI Sarah Leigh changed review comment from: Comment on list classification: The gene / disease association has been recently been revoked on OMIM as the reported variant (rs11909217) is present in 1,382 of 282,752 alleles and in 8 homozygotes in the gnomAD database (Personal communication to OMIM by Ada Hamosh June 25, 2019).; to: Comment on list classification: The gene / disease association has been recently been revoked on OMIM as the reclassified variant (rs11909217) is present in 1,382 of 282,752 alleles and in 8 homozygotes in the gnomAD database (Personal communication to OMIM by Ada Hamosh June 25, 2019).
Adult onset neurodegenerative disorder v1.56 DAB1 Louise Daugherty Publications for gene: DAB1 were set to 28686858
Adult onset neurodegenerative disorder v1.55 C9orf72 Louise Daugherty Publications for gene: C9orf72 were set to 27059391; 25638642; PMID: 21944778; 23597494; 21944779; http://www.ncbi.nlm.nih.gov/pubmed/25326098; 25326098
Adult onset neurodegenerative disorder v1.54 ATP2B3 Louise Daugherty Publications for gene: ATP2B3 were set to
Adult onset neurodegenerative disorder v1.53 ARX Louise Daugherty Publications for gene: ARX were set to
Adult onset neurodegenerative disorder v1.52 ATP8A2 Louise Daugherty Publications for gene: ATP8A2 were set to PMID: 22892528
Adult onset neurodegenerative disorder v1.51 CLP1 Louise Daugherty Phenotypes for gene: CLP1 were changed from Pontocerebellar hypoplasia 10 (#615803) to Pontocerebellar hypoplasia 10, 615803
Adult onset neurodegenerative disorder v1.50 CLP1 Louise Daugherty Publications for gene: CLP1 were set to
Ophthalmological ciliopathies v0.1 TULP1 Ivone Leong gene: TULP1 was added
gene: TULP1 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: TULP1 was set to
Phenotypes for gene: TULP1 were set to Retinitis pigmentosa 14, 600132; Leber congenital amaurosis 15, 613843; Ciliopathies
Ophthalmological ciliopathies v0.1 TRIM32 Ivone Leong gene: TRIM32 was added
gene: TRIM32 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list,Expert Review Red,UKGTN
Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM32 were set to 11822024; 16606853
Phenotypes for gene: TRIM32 were set to ?Bardet-Biedl syndrome 11, 615988; Muscular dystrophy, limb-girdle, type 2H, 254110
Ophthalmological ciliopathies v0.1 TOPORS Ivone Leong gene: TOPORS was added
gene: TOPORS was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: TOPORS was set to
Phenotypes for gene: TOPORS were set to Ciliopathies
Ophthalmological ciliopathies v0.1 TBC1D32 Ivone Leong gene: TBC1D32 was added
gene: TBC1D32 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: TBC1D32 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D32 were set to No OMIM phenotype; Oro-facio-digital syndrome type IX (Adly (2014) Hum Mutat 35, 36)
Ophthalmological ciliopathies v0.1 SPATA7 Ivone Leong gene: SPATA7 was added
gene: SPATA7 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: SPATA7 was set to
Phenotypes for gene: SPATA7 were set to Leber congenital amaurosis 3, 604232; Ciliopathies; Retinitis pigmentosa, juvenile, autosomal recessive, 604232
Ophthalmological ciliopathies v0.1 RPGRIP1 Ivone Leong gene: RPGRIP1 was added
gene: RPGRIP1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Orphanet,Expert Review Red
Mode of inheritance for gene: RPGRIP1 was set to
Phenotypes for gene: RPGRIP1 were set to Meckel syndrome; Ciliopathies
Ophthalmological ciliopathies v0.1 RPE65 Ivone Leong gene: RPE65 was added
gene: RPE65 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: RPE65 was set to
Phenotypes for gene: RPE65 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 RDH12 Ivone Leong gene: RDH12 was added
gene: RDH12 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: RDH12 was set to
Phenotypes for gene: RDH12 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 RD3 Ivone Leong gene: RD3 was added
gene: RD3 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: RD3 was set to
Phenotypes for gene: RD3 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 PIBF1 Ivone Leong gene: PIBF1 was added
gene: PIBF1 was added to Ophthalmological ciliopathies. Sources: Research,Literature,Expert Review Red,Expert Review
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768
Phenotypes for gene: PIBF1 were set to Joubert syndrome; ataxia; vermis hypoplasia; developmental delay; thick superior cerebellar peduncles; superior cerebellar dysplasia
Ophthalmological ciliopathies v0.1 PDE6D Ivone Leong gene: PDE6D was added
gene: PDE6D was added to Ophthalmological ciliopathies. Sources: UKGTN,Other,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: PDE6D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6D were set to 24166846
Phenotypes for gene: PDE6D were set to ?Joubert syndrome 22; Joubert Syndrome and Senior-Loken Syndrome 24 gene panel; ?Joubert syndrome 22, 615665
Ophthalmological ciliopathies v0.1 LRAT Ivone Leong gene: LRAT was added
gene: LRAT was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: LRAT was set to
Phenotypes for gene: LRAT were set to Ciliopathies
Ophthalmological ciliopathies v0.1 LCA5 Ivone Leong gene: LCA5 was added
gene: LCA5 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: LCA5 was set to
Phenotypes for gene: LCA5 were set to Leber congenital amaurosis 5, 604537; Ciliopathies
Ophthalmological ciliopathies v0.1 KIAA0556 Ivone Leong gene: KIAA0556 was added
gene: KIAA0556 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KIAA0556 were set to ?Joubert syndrome 26
Ophthalmological ciliopathies v0.1 KCNJ13 Ivone Leong gene: KCNJ13 was added
gene: KCNJ13 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: KCNJ13 was set to
Phenotypes for gene: KCNJ13 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 IMPDH1 Ivone Leong gene: IMPDH1 was added
gene: IMPDH1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: IMPDH1 was set to
Phenotypes for gene: IMPDH1 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 IFT74 Ivone Leong gene: IFT74 was added
gene: IFT74 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 27486776
Phenotypes for gene: IFT74 were set to ?Bardet-Biedl syndrome 20, 617119
Ophthalmological ciliopathies v0.1 GUCY2D Ivone Leong gene: GUCY2D was added
gene: GUCY2D was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: GUCY2D was set to
Phenotypes for gene: GUCY2D were set to Ciliopathies
Ophthalmological ciliopathies v0.1 EXOC8 Ivone Leong gene: EXOC8 was added
gene: EXOC8 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert Review Red
Mode of inheritance for gene: EXOC8 was set to
Publications for gene: EXOC8 were set to 22700954
Phenotypes for gene: EXOC8 were set to No OMIM phenotype; Joubert syndrome (Dixon-Salazar (2012) Sci Transl Med 4, 138ra78)
Ophthalmological ciliopathies v0.1 CRX Ivone Leong gene: CRX was added
gene: CRX was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: CRX was set to
Phenotypes for gene: CRX were set to Ciliopathies
Ophthalmological ciliopathies v0.1 CRB1 Ivone Leong gene: CRB1 was added
gene: CRB1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: CRB1 was set to
Phenotypes for gene: CRB1 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 CCDC28B Ivone Leong gene: CCDC28B was added
gene: CCDC28B was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list,Expert Review Red,UKGTN
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 23015189
Phenotypes for gene: CCDC28B were set to ciliopathies; {Bardet-Biedl syndrome 1, modifier of}, 209900
Ophthalmological ciliopathies v0.1 C8orf37 Ivone Leong gene: C8orf37 was added
gene: C8orf37 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Red
Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C8orf37 were set to 26854863; 27008867
Phenotypes for gene: C8orf37 were set to Bardet-Biedl syndrome 21, 617406
Ophthalmological ciliopathies v0.1 C2orf71 Ivone Leong gene: C2orf71 was added
gene: C2orf71 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: C2orf71 was set to
Phenotypes for gene: C2orf71 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 BBIP1 Ivone Leong gene: BBIP1 was added
gene: BBIP1 was added to Ophthalmological ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red
Mode of inheritance for gene: BBIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBIP1 were set to 24026985
Phenotypes for gene: BBIP1 were set to ?Bardet-Biedl syndrome 18, 615995
Ophthalmological ciliopathies v0.1 B9D1 Ivone Leong gene: B9D1 was added
gene: B9D1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D1 were set to 21493627; 25920555; 24886560
Phenotypes for gene: B9D1 were set to ?Meckel syndrome 9, 614209; ciliopathies; Meckel syndrome; Joubert syndrome 27
Ophthalmological ciliopathies v0.1 AIPL1 Ivone Leong gene: AIPL1 was added
gene: AIPL1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert Review Red
Mode of inheritance for gene: AIPL1 was set to
Phenotypes for gene: AIPL1 were set to Ciliopathies
Ophthalmological ciliopathies v0.1 RPGR Ivone Leong gene: RPGR was added
gene: RPGR was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,Expert Review Red
Mode of inheritance for gene: RPGR was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ophthalmological ciliopathies v0.1 WDR19 Ivone Leong gene: WDR19 was added
gene: WDR19 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: WDR19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR19 were set to Nephronophthisis 13, 614377; ?Short-rib thoracic dysplasia 5 with or without polydactyly; Senior-Loken syndrome 8, 616307; Cranioectodermal dysplasia; ?Short-rib thoracic dysplasia 5 with or without polydactyly, 614376; Jeune syndrome; Senior-Loken syndrome; ?Cranioectodermal dysplasia 4, 614378; Nephronophthisis
Ophthalmological ciliopathies v0.1 WDPCP Ivone Leong gene: WDPCP was added
gene: WDPCP was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: WDPCP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDPCP were set to 20671153
Phenotypes for gene: WDPCP were set to ?Bardet-Biedl syndrome 15, 615992; Meckel syndrome; ?Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Ophthalmological ciliopathies v0.1 VPS13B Ivone Leong gene: VPS13B was added
gene: VPS13B was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13B were set to Cohen syndrome, 216550; COHEN SYNDROME
Ophthalmological ciliopathies v0.1 TTC8 Ivone Leong gene: TTC8 was added
gene: TTC8 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC8 were set to 14520415
Phenotypes for gene: TTC8 were set to Bardet Biedl syndrome 8
Ophthalmological ciliopathies v0.1 TRAF3IP1 Ivone Leong gene: TRAF3IP1 was added
gene: TRAF3IP1 was added to Ophthalmological ciliopathies. Sources: Orphanet,Expert Review Green
Mode of inheritance for gene: TRAF3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAF3IP1 were set to 26487268
Phenotypes for gene: TRAF3IP1 were set to Senior-Loken syndrome 9 616629
Ophthalmological ciliopathies v0.1 TMEM67 Ivone Leong gene: TMEM67 was added
gene: TMEM67 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: TMEM67 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM67 were set to 20607301; 17160906; 18327255; 19058225; 19508969; 16415887
Phenotypes for gene: TMEM67 were set to Joubert syndrome; nephronophthisis; COACH syndrome; Joubert syndrome 6; ?Bardet-Biedl syndrome?; Senior-Boichis syndrome; 613550; 607361; Meckel-Gruber syndrome; Meckel syndrome; 610688; Nephronophthisis 11; 216360
Ophthalmological ciliopathies v0.1 TMEM237 Ivone Leong gene: TMEM237 was added
gene: TMEM237 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TMEM237 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM237 were set to 22152675; 20301500
Phenotypes for gene: TMEM237 were set to Joubert syndrome; Joubert syndrome with oculorenal defect; Joubert syndrome 14
Ophthalmological ciliopathies v0.1 TMEM231 Ivone Leong gene: TMEM231 was added
gene: TMEM231 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: TMEM231 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM231 were set to Meckel syndrome; Joubert syndrome 20; Joubert syndrome with oculorenal defect; Joubert syndrome 20, 614970; Meckel syndrome 11, 615397
Ophthalmological ciliopathies v0.1 TMEM216 Ivone Leong gene: TMEM216 was added
gene: TMEM216 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TMEM216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM216 were set to 22282472; 20036350; 20512146
Phenotypes for gene: TMEM216 were set to Joubert syndrome: Meckel-Gruber syndrome; Joubert syndrome with oculorenal defect; Meckel syndrome; Joubert syndrome 2
Ophthalmological ciliopathies v0.1 TMEM138 Ivone Leong gene: TMEM138 was added
gene: TMEM138 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TMEM138 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM138 were set to 22282472
Phenotypes for gene: TMEM138 were set to Joubert syndrome with oculorenal defect; Joubert syndrome 16
Ophthalmological ciliopathies v0.1 TMEM107 Ivone Leong gene: TMEM107 was added
gene: TMEM107 was added to Ophthalmological ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM107 were set to 26518474; 26123494; 22698544; 26595381
Phenotypes for gene: TMEM107 were set to Meckel syndrome 13, 617562; ?Joubert syndrome 29, 617562; Orofaciodigital syndrome XVI, 617563
Ophthalmological ciliopathies v0.1 TCTN3 Ivone Leong gene: TCTN3 was added
gene: TCTN3 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTN3 were set to 25118024; 22883145
Phenotypes for gene: TCTN3 were set to Joubert syndrome; Orofaciodigital syndrome IV; Joubert syndrome 18; Meckel-Gruber; Mohr-Majewski syndrome
Ophthalmological ciliopathies v0.1 TCTN2 Ivone Leong gene: TCTN2 was added
gene: TCTN2 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: TCTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTN2 were set to 25118024; 21565611
Phenotypes for gene: TCTN2 were set to Meckel syndrome; Joubert syndrome 24; Joubert syndrome, Meckel-Gruber syndrome
Ophthalmological ciliopathies v0.1 TCTN1 Ivone Leong gene: TCTN1 was added
gene: TCTN1 was added to Ophthalmological ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TCTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCTN1 were set to 20301500; 22693042; 26489806; 21725307; 26477546; 28631893
Phenotypes for gene: TCTN1 were set to Joubert syndrome
Ophthalmological ciliopathies v0.1 SDCCAG8 Ivone Leong gene: SDCCAG8 was added
gene: SDCCAG8 was added to Ophthalmological ciliopathies. Sources: Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: SDCCAG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDCCAG8 were set to 22190896
Phenotypes for gene: SDCCAG8 were set to SENIOR-LOKEN SYNDROME; Bardet-Biedl Syndrome; 613615; Senior-Loken syndrome
Ophthalmological ciliopathies v0.1 SCLT1 Ivone Leong gene: SCLT1 was added
gene: SCLT1 was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to 15797711
Phenotypes for gene: SCLT1 were set to Oro-facio-digital syndrome type IX (Adly (2014) Hum Mutat 35,36); No OMIM phenotype
Ophthalmological ciliopathies v0.1 RPGRIP1L Ivone Leong gene: RPGRIP1L was added
gene: RPGRIP1L was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: RPGRIP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPGRIP1L were set to 17558409; 17558407; 19574260
Phenotypes for gene: RPGRIP1L were set to Joubert syndrome 7; Meckel syndrome 5; Joubert syndrome; Meckel syndrome; Meckel-Gruber syndrome
Ophthalmological ciliopathies v0.1 PMM2 Ivone Leong gene: PMM2 was added
gene: PMM2 was added to Ophthalmological ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 9140401
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia 212065
Ophthalmological ciliopathies v0.1 OFD1 Ivone Leong gene: OFD1 was added
gene: OFD1 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: OFD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: OFD1 were set to 19800048; 22353940
Phenotypes for gene: OFD1 were set to Joubert syndrome 10; X-linked Joubert syndrome; Orofaciodigital syndrome I
Ophthalmological ciliopathies v0.1 NPHP4 Ivone Leong gene: NPHP4 was added
gene: NPHP4 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NPHP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP4 were set to Senior-Loken syndrome; Nephronophthisis; Senior-Loken syndrome 4, 606996; Nephronophthisis 4, 606966
Ophthalmological ciliopathies v0.1 NPHP3 Ivone Leong gene: NPHP3 was added
gene: NPHP3 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NPHP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP3 were set to Renal-hepatic-pancreatic dysplasia; Senior-Loken syndrome; Nephronophthisis 3, 604387; Meckel syndrome 7, 267010; Renal-hepatic-pancreatic dysplasia 1, 208540; Nephronophthisis
Ophthalmological ciliopathies v0.1 NPHP1 Ivone Leong gene: NPHP1 was added
gene: NPHP1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: NPHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPHP1 were set to 15138899; 22982934; 15689444
Phenotypes for gene: NPHP1 were set to Joubert syndrome 4; Senior-Loken syndrome; 256100 Senior-Loken syndrome-1, 266900; 609583 Nephronophthisis 1, juvenile; Nephronophthisis
Ophthalmological ciliopathies v0.1 MKS1 Ivone Leong gene: MKS1 was added
gene: MKS1 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: MKS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKS1 were set to 26490104; 17437276; 18327255; 24886560; 16415886
Phenotypes for gene: MKS1 were set to occipital encephalocele; Joubert syndrome; Bardet-Biedl syndrome; Joubert syndrome 28; 249000; polydactyly; polycystic kidneys; Meckel-Gruber syndrome; Meckel syndrome; renal fibrosis
Ophthalmological ciliopathies v0.1 MKKS Ivone Leong gene: MKKS was added
gene: MKKS was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: MKKS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKKS were set to 10802661; 10973251; 10973238
Phenotypes for gene: MKKS were set to Bardet Biedl syndrome 6; 236700
Ophthalmological ciliopathies v0.1 LZTFL1 Ivone Leong gene: LZTFL1 was added
gene: LZTFL1 was added to Ophthalmological ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 27312011; 23692385
Phenotypes for gene: LZTFL1 were set to Bardet-Biedl syndrome 17, 615994
Ophthalmological ciliopathies v0.1 KIF7 Ivone Leong gene: KIF7 was added
gene: KIF7 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: KIF7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF7 were set to 21633164
Phenotypes for gene: KIF7 were set to Joubert syndrome 12 200990; Acrocallosal syndrome 200990
Ophthalmological ciliopathies v0.1 KIAA0586 Ivone Leong gene: KIAA0586 was added
gene: KIAA0586 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to 26096313
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23; Joubert syndrome; Short-rib thoracic dysplasia 14 with polydactyly; Short-rib dysplasia 14 with polydactyly
Ophthalmological ciliopathies v0.1 IQCB1 Ivone Leong gene: IQCB1 was added
gene: IQCB1 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: IQCB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IQCB1 were set to Senior-Loken syndrome 5, 609254; Senior-Loken syndrome
Ophthalmological ciliopathies v0.1 INPP5E Ivone Leong gene: INPP5E was added
gene: INPP5E was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: INPP5E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP5E were set to 23386033; 26748598
Phenotypes for gene: INPP5E were set to Joubert syndrome; Joubert syndrome 1
Ophthalmological ciliopathies v0.1 IFT172 Ivone Leong gene: IFT172 was added
gene: IFT172 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: IFT172 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT172 were set to 24140113
Phenotypes for gene: IFT172 were set to Retinitis pigmentosa 71, 616394; Short-rib thoracic dysplasia 10 with or without polydactyly; Saldino-Mainzer syndrome; Jeune syndrome; Short-rib thoracic dysplasia 10 with or without polydactyly, 615630
Ophthalmological ciliopathies v0.1 HYLS1 Ivone Leong gene: HYLS1 was added
gene: HYLS1 was added to Ophthalmological ciliopathies. Sources: UKGTN,Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: HYLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYLS1 were set to 18648327; 26830932; 19656802; 15843405
Phenotypes for gene: HYLS1 were set to Joubert syndrome; Hydrolethalus syndrome, 236680
Ophthalmological ciliopathies v0.1 GLI3 Ivone Leong gene: GLI3 was added
gene: GLI3 was added to Ophthalmological ciliopathies. Sources: UKGTN,Expert list,Expert Review Green
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GLI3 were set to Joubert Syndrome and Senior-Loken Syndrome 24 gene panel
Ophthalmological ciliopathies v0.1 DDX59 Ivone Leong gene: DDX59 was added
gene: DDX59 was added to Ophthalmological ciliopathies. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to 29127725; 23972372; 28711741
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, 174300
Ophthalmological ciliopathies v0.1 CSPP1 Ivone Leong gene: CSPP1 was added
gene: CSPP1 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green,Orphanet
Mode of inheritance for gene: CSPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSPP1 were set to 24360807; 24360803; 24360808
Phenotypes for gene: CSPP1 were set to Joubert syndrome; Meckel syndrome; Joubert syndrome 21; Meckel-Gruber syndrome
Ophthalmological ciliopathies v0.1 CEP41 Ivone Leong gene: CEP41 was added
gene: CEP41 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: CEP41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP41 were set to 22246503
Phenotypes for gene: CEP41 were set to Joubert syndrome 15
Ophthalmological ciliopathies v0.1 CEP290 Ivone Leong gene: CEP290 was added
gene: CEP290 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: CEP290 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP290 were set to 20690115; 18327255
Phenotypes for gene: CEP290 were set to 610189; Meckel syndrome 4; Senior-Loken syndrome; 611755; Joubert syndrome 5; Joubert syndrome with oculorenal defect; 610188; Senior-Loken syndrome 6; 611134; Meckel syndrome
Ophthalmological ciliopathies v0.1 CEP164 Ivone Leong gene: CEP164 was added
gene: CEP164 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: CEP164 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP164 were set to ciliopathies; Nephronophthisis 15; Senior-Loken syndrome; Nephronophthisis 15, 614845
Ophthalmological ciliopathies v0.1 CEP104 Ivone Leong gene: CEP104 was added
gene: CEP104 was added to Ophthalmological ciliopathies. Sources: Other,Radboud University Medical Center, Nijmegen,Expert Review Green
Mode of inheritance for gene: CEP104 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP104 were set to 26477546
Phenotypes for gene: CEP104 were set to Joubert syndrome 25, 616781; Joubert syndrome 25
Ophthalmological ciliopathies v0.1 CENPF Ivone Leong gene: CENPF was added
gene: CENPF was added to Ophthalmological ciliopathies. Sources: Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to 26820108
Phenotypes for gene: CENPF were set to Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Ophthalmological ciliopathies v0.1 CC2D2A Ivone Leong gene: CC2D2A was added
gene: CC2D2A was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing,Orphanet
Mode of inheritance for gene: CC2D2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CC2D2A were set to Joubert syndrome 9; COACH syndrome; Joubert syndrome with oculorenal defect; Meckel syndrome 6; Meckel syndrome
Ophthalmological ciliopathies v0.1 C5orf42 Ivone Leong gene: C5orf42 was added
gene: C5orf42 was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: C5orf42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C5orf42 were set to 22693042; 25920555; 22425360
Phenotypes for gene: C5orf42 were set to Joubert syndrome; Oral-facial-digital syndrome type VI; Joubert syndrome 17
Ophthalmological ciliopathies v0.1 C21orf2 Ivone Leong gene: C21orf2 was added
gene: C21orf2 was added to Ophthalmological ciliopathies. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: C21orf2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C21orf2 were set to 26974433; 27548899; 23105016; 26167768
Phenotypes for gene: C21orf2 were set to Jeune asphyxiating thoracic dystrophy (JATD); Jeune Syndrome; Spondylometaphyseal dysplasia, axial, 602271; Retinal dystrophy with macular staphyloma, 617547
Ophthalmological ciliopathies v0.1 BBS9 Ivone Leong gene: BBS9 was added
gene: BBS9 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS9 were set to 16380913
Phenotypes for gene: BBS9 were set to Bardet Biedl syndrome 9
Ophthalmological ciliopathies v0.1 BBS7 Ivone Leong gene: BBS7 was added
gene: BBS7 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS7 were set to 12567324
Phenotypes for gene: BBS7 were set to Bardet Biedl syndrome 7
Ophthalmological ciliopathies v0.1 BBS5 Ivone Leong gene: BBS5 was added
gene: BBS5 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS5 were set to 15137946
Phenotypes for gene: BBS5 were set to Bardet Biedl syndrome 5
Ophthalmological ciliopathies v0.1 BBS4 Ivone Leong gene: BBS4 was added
gene: BBS4 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS4 were set to 11381270; 22353939
Phenotypes for gene: BBS4 were set to Bardet Biedl syndrome 4
Ophthalmological ciliopathies v0.1 BBS2 Ivone Leong gene: BBS2 was added
gene: BBS2 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS2 were set to 11285252
Phenotypes for gene: BBS2 were set to Bardet Biedl syndrome 2
Ophthalmological ciliopathies v0.1 BBS12 Ivone Leong gene: BBS12 was added
gene: BBS12 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS12 were set to 17160889
Phenotypes for gene: BBS12 were set to Bardet Biedl syndrome 12
Ophthalmological ciliopathies v0.1 BBS10 Ivone Leong gene: BBS10 was added
gene: BBS10 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS10 were set to 16582908
Phenotypes for gene: BBS10 were set to Bardet Biedl syndrome 10
Ophthalmological ciliopathies v0.1 BBS1 Ivone Leong gene: BBS1 was added
gene: BBS1 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: BBS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS1 were set to 23143442; 12118255
Phenotypes for gene: BBS1 were set to Bardet Biedl syndrome 13; 268000; Bardet Biedl syndrome 1; Bardet Biedl syndrome 11
Ophthalmological ciliopathies v0.1 B9D2 Ivone Leong gene: B9D2 was added
gene: B9D2 was added to Ophthalmological ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: B9D2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D2 were set to 21763481; 26092869
Phenotypes for gene: B9D2 were set to Joubert syndrome; Meckel syndrome 10, 614175; ciliopathies; Meckel syndrome
Ophthalmological ciliopathies v0.1 ARMC9 Ivone Leong gene: ARMC9 was added
gene: ARMC9 was added to Ophthalmological ciliopathies. Sources: Literature,Expert Review Green
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to 28625504
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30, 617622
Ophthalmological ciliopathies v0.1 ARL6 Ivone Leong gene: ARL6 was added
gene: ARL6 was added to Ophthalmological ciliopathies. Sources: Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: ARL6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6 were set to 15258860; 21282186
Phenotypes for gene: ARL6 were set to {Bardet Biedl syndrome 1, modifier of}; Bardet-Biedl Syndrome; 268000; Bardet Biedl syndrome 3
Ophthalmological ciliopathies v0.1 ARL13B Ivone Leong gene: ARL13B was added
gene: ARL13B was added to Ophthalmological ciliopathies. Sources: Other,Expert list,Expert Review Green
Mode of inheritance for gene: ARL13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL13B were set to 18674751; 25138100
Phenotypes for gene: ARL13B were set to Joubert syndrome 8
Ophthalmological ciliopathies v0.1 ALMS1 Ivone Leong gene: ALMS1 was added
gene: ALMS1 was added to Ophthalmological ciliopathies. Sources: Expert list,UKGTN,Eligibility statement prior genetic testing,Orphanet,Expert Review Green,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALMS1 were set to 22773737
Phenotypes for gene: ALMS1 were set to Alstrom Syndrome; Bardet-Biedl Syndrome; 203800; Alstrom syndrome
Ophthalmological ciliopathies v0.1 AHI1 Ivone Leong gene: AHI1 was added
gene: AHI1 was added to Ophthalmological ciliopathies. Sources: Other,Expert Review Green,Expert list,Eligibility statement prior genetic testing
Mode of inheritance for gene: AHI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AHI1 were set to Joubert syndrome 3; Joubert syndrome; Joubert syndrome-3.
Early onset or syndromic epilepsy v1.132 KCNMA1 Rebecca Foulger Added comment: Comment on phenotypes: MIM:617643 has AR inheritance in OMIM. MIM:609446 has monoallelic inheritance in OMIM.
Early onset or syndromic epilepsy v1.132 KCNMA1 Rebecca Foulger Phenotypes for gene: KCNMA1 were changed from ?Cerebellar atrophy, developmental delay, and seizures 617643 AR; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy 609446 AD to ?Cerebellar atrophy, developmental delay, and seizures, 617643; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, 609446
Early onset or syndromic epilepsy v1.131 KCNMA1 Rebecca Foulger Publications for gene: KCNMA1 were set to 15937479; 26195193; 27567911
Early onset or syndromic epilepsy v1.130 KCNMA1 Rebecca Foulger commented on gene: KCNMA1: PMID:29545233. Yesil et al., 2018 report a patient with a novel homozygous truncating variant in KCNMA1 (p.Arg458Ter) presentint with paroxysmal dyskinesia, epileptic seizures, ID, and corticospinal–cerebellar tract atrophy.
Early onset or syndromic epilepsy v1.130 KCNMA1 Rebecca Foulger commented on gene: KCNMA1: PMID:15937479. Du et al., 2005 studied a large family with generalized epilepsy and paroxysmal dyskinesia (GEPD). 5/16 had seizures + paroxysmal dyskinesia (PNKD), and a further 4/16 had seizures only. c.1301A>G (Asp434Gly). They identified a heterozygous c.1301A>G (Asp434Gly) in KCNMA1 in the proband (IV-8) of the family and in all 13 affected individuals that were genotyped. The variant was absent in 5 unaffected individuals.
Rare multisystem ciliopathy disorders v1.119 IFT43 Rebecca Foulger Deleted their comment
Rare multisystem ciliopathy disorders v1.119 IFT43 Rebecca Foulger commented on gene: IFT43: PMID:26195193. Zhang et al 2015 describe 2 unrelated children with early-onset PNKD and developmental delay carrying de novo mutations in KCNMA1. Seizures were not reported until age 2 and 7. Two de novo heterozygous missense mutations in KCNMA1 were identified in these cases: c.2650G>A (p.Glu884Lys) and c.3158A>G (p.Asn1053Ser).
Early onset or syndromic epilepsy v1.130 KCNMA1 Rebecca Foulger commented on gene: KCNMA1: PMID:26195193. Zhang et al 2015 describe 2 unrelated children with early-onset PNKD and developmental delay carrying de novo mutations in KCNMA1. Seizures were not reported until age 2 and 7. Two de novo heterozygous missense mutations in KCNMA1 were identified in these cases: c.2650G>A (p.Glu884Lys) and c.3158A>G (p.Asn1053Ser).
Early onset or syndromic epilepsy v1.130 KCNMA1 Rebecca Foulger commented on gene: KCNMA1
Early onset or syndromic epilepsy v1.130 DOLK Rebecca Foulger Classified gene: DOLK as Green List (high evidence)
Early onset or syndromic epilepsy v1.130 DOLK Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on external review by Konstantinos Varvagiannis, the third case of seizures reported in PMID:24144945, and the review of seizure phenotypes also reported by PMID:24144945. Although seizures are not reported in all patients, the association of CDG is confirmed in DDG2P, seizures can be severe, and there are sufficient cases for inclusion on panel.
Early onset or syndromic epilepsy v1.130 DOLK Rebecca Foulger Gene: dolk has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.129 DOLK Rebecca Foulger Publications for gene: DOLK were set to 23890587; 17273964
Fetal anomalies v0.298 DOLK Rebecca Foulger Mode of pathogenicity for gene: DOLK was changed from to Other
Fetal anomalies v0.297 DOLK Rebecca Foulger Publications for gene: DOLK were set to
Early onset or syndromic epilepsy v1.128 DOLK Rebecca Foulger commented on gene: DOLK: PMID:28816422 (Rush et al., 2017) report 2 sisters with novel compound het DOLK variants: c.951C>A (p.Tyr317Ter) and c.1558A>G (p.Thr520Ala). Patient 2 had one seizure at 53 days old- the seizures did not recur and the patient died age 64 days. Seizures were not noted for her sister (Patient 1), although she died at just over a week old.
Early onset or syndromic epilepsy v1.128 DOLK Rebecca Foulger commented on gene: DOLK: PMID:24144945 (Lieu et al., 2013) report a male neonate born to non-consanguineous Palestinian origin parents, with phenotypes including dysmorphic features, genital abnormalities, talipes equinovarus, and severe refractory generalized seizures. He harboured a homozygous p.Q483K DOLK variant- in patient fibroblasts this missense variant severely reduced substrate binding and cataytic activity. They also summarise clinical data of previous DOLK-CDG patients, and report seizures in 7/18 patients (Table 1 and article text).
Differences in sex development v1.35 ZFPM2 Martina Owens reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24549039, 27899157, 12223418; Phenotypes: 46XY sex reversal 9 616067; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ophthalmological ciliopathies v0.0 Ivone Leong Added Panel Ophthalmological ciliopathies
Set panel types to: GMS Rare Disease Virtual
Hereditary ataxia with onset in adulthood v1.178 TBP_CAG Louise Daugherty Source London North GLH was added to STR: TBP_CAG.
Hereditary ataxia with onset in adulthood v1.178 PPP2R2B_CAG Louise Daugherty Source London North GLH was added to STR: PPP2R2B_CAG.
Hereditary ataxia with onset in adulthood v1.178 NOP56_GGCCTG Louise Daugherty Source London North GLH was added to STR: NOP56_GGCCTG.
Hereditary ataxia with onset in adulthood v1.178 HTT_CAG Louise Daugherty Source London North GLH was added to STR: HTT_CAG.
Hereditary ataxia with onset in adulthood v1.178 FXN_GAA Louise Daugherty Source London North GLH was added to STR: FXN_GAA.
Hereditary ataxia with onset in adulthood v1.178 CACNA1A_CAG Louise Daugherty Source London North GLH was added to STR: CACNA1A_CAG.
Hereditary ataxia with onset in adulthood v1.178 ATXN7_CAG Louise Daugherty Source London North GLH was added to STR: ATXN7_CAG.
Hereditary ataxia with onset in adulthood v1.178 ATXN3_CAG Louise Daugherty Source London North GLH was added to STR: ATXN3_CAG.
Hereditary ataxia with onset in adulthood v1.178 ATXN2_CAG Louise Daugherty Source London North GLH was added to STR: ATXN2_CAG.
Hereditary ataxia with onset in adulthood v1.178 ATXN1_CAG Louise Daugherty Source London North GLH was added to STR: ATXN1_CAG.
Hereditary ataxia with onset in adulthood v1.178 ATXN10_ATTCT Louise Daugherty Source London North GLH was added to STR: ATXN10_ATTCT.
Hereditary ataxia with onset in adulthood v1.178 ATN1_CAG Louise Daugherty Source London North GLH was added to STR: ATN1_CAG.
Hereditary ataxia with onset in adulthood v1.177 ATXN7_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.177 ATXN3_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.177 HTT_CAG Louise Daugherty Source NHS GMS was added to STR: HTT_CAG.
Hereditary ataxia with onset in adulthood v1.177 CACNA1A_CAG Louise Daugherty Source NHS GMS was added to STR: CACNA1A_CAG.
Hereditary ataxia with onset in adulthood v1.177 ATXN7_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN7_CAG.
Hereditary ataxia with onset in adulthood v1.177 ATXN3_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN3_CAG.
Hereditary ataxia with onset in adulthood v1.177 ATXN2_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN2_CAG.
Hereditary ataxia with onset in adulthood v1.177 ATXN1_CAG Louise Daugherty Source NHS GMS was added to STR: ATXN1_CAG.
Hereditary ataxia with onset in adulthood v1.177 ATXN10_ATTCT Louise Daugherty Source NHS GMS was added to STR: ATXN10_ATTCT.
Hereditary ataxia with onset in adulthood v1.177 ATN1_CAG Louise Daugherty Source NHS GMS was added to STR: ATN1_CAG.
Hereditary ataxia with onset in adulthood v1.176 HTT_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: HTT_CAG.
Hereditary ataxia with onset in adulthood v1.176 CACNA1A_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: CACNA1A_CAG.
Hereditary ataxia with onset in adulthood v1.176 ATXN7_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: ATXN7_CAG.
Hereditary ataxia with onset in adulthood v1.176 ATXN3_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: ATXN3_CAG.
Hereditary ataxia with onset in adulthood v1.176 ATXN2_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: ATXN2_CAG.
Hereditary ataxia with onset in adulthood v1.176 ATXN1_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: ATXN1_CAG.
Hereditary ataxia with onset in adulthood v1.176 ATXN10_ATTCT Louise Daugherty Source Wessex and West Midlands GLH was added to STR: ATXN10_ATTCT.
Hereditary ataxia with onset in adulthood v1.176 ATN1_CAG Louise Daugherty Source Wessex and West Midlands GLH was added to STR: ATN1_CAG.
Publications for STR: ATN1_CAG were changed from 20301664; 8136840; 20301664; 8136840; 8136826; 7614090 to 20301664; 8136826; 8136840; 7614090
Hereditary ataxia with onset in adulthood v1.175 NOP56 Louise Daugherty Classified gene: NOP56 as Red List (low evidence)
Hereditary ataxia with onset in adulthood v1.175 NOP56 Louise Daugherty Gene: nop56 has been classified as Red List (Low Evidence).
Hereditary ataxia with onset in adulthood v1.174 NOP56 Louise Daugherty changed review comment from: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group; to: Review and rating submitted byJames Polke, on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.174 NOP56 Louise Daugherty edited their review of gene: NOP56: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from James Polke on behalf of London North GLH for GMS Neurology specialist test group relates to the STR and not the gene entity (and is indicated in his comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Intellectual disability v2.938 CTBP1 Konstantinos Varvagiannis changed review comment from: 12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article:
- Beck et al. 2016 (PMID: 27094857) : 4 individuals
- Sommerville et al. 2017 (PMID: 28955726) : 1 subject
- Beck et al. 2019 (PMID: 31041561) : 7 further individuals

Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on.

A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect.

Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism.

Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders).

Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1).

Role and Functional studies:
- The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884).
- In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors.
- RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated).
- Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this.
- Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies.

Animal models:
- Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226)
- As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential.

----
CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P.
Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability.
----

As a result, CTBP1 can be added in the current panel probably as green.; to: 12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article:
- Beck et al. 2016 (PMID: 27094857) : 4 individuals
- Sommerville et al. 2017 (PMID: 28955726) : 1 subject
- Beck et al. 2019 (PMID: 31041561) : 7 further individuals

Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on.

A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect.

Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism.

Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders).

Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1).

Role and Functional studies:
- The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884).
- In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors.
- RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated).
- Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this.
- Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies.

Animal models:
- Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226)
- As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential (Cited: Kim and Youn 2009 - PMID: 19136938).

----
CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P.
Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability.
----

As a result, CTBP1 can be added in the current panel probably as green.
Hereditary ataxia with onset in adulthood v1.174 ATXN2_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.174 ATXN10_ATTCT Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.174 ATN1_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group. Comment: DRPLA. Triplet repeat. Asked for by Prof Giunti sometimes with ataxia patients with signs of dementia etc.; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group. Comment: DRPLA. Triplet repeat. Asked for by Prof Giunti sometimes with ataxia patients with signs of dementia etc.
Intellectual disability v2.938 CTBP1 Konstantinos Varvagiannis reviewed gene: CTBP1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 27094857, 28955726, 31041561; Phenotypes: Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (MIM 617915); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Intellectual disability v2.938 CTBP1 Konstantinos Varvagiannis Deleted their review
Intellectual disability v2.938 CTBP1 Konstantinos Varvagiannis changed review comment from: 12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article:
- Beck et al. 2016 (PMID: 27094857) : 4 individuals
- Sommerville et al. 2017 (PMID: 28955726) : 1 subject
- Beck et al. 2019 (PMID: 31041561) : 7 further individuals

Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on.

A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect.

Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism.

Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders).

Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1 ).

Role and Functional studies:
- The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884).
- In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors.
- RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated).
- Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this.
- Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies.

Animal models:
- Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226)
- As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential.

----
CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P.
Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability.
----

As a result, CTBP1 can be added in the current panel probably as green.
Sources: Literature; to: 12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article:
- Beck et al. 2016 (PMID: 27094857) : 4 individuals
- Sommerville et al. 2017 (PMID: 28955726) : 1 subject
- Beck et al. 2019 (PMID: 31041561) : 7 further individuals

Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on.

A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect.

Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism.

Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders).

Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1).

Role and Functional studies:
- The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884).
- In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors.
- RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated).
- Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this.
- Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies.

Animal models:
- Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226)
- As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential.

----
CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P.
Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability.
----

As a result, CTBP1 can be added in the current panel probably as green.
Sources: Literature
Intellectual disability v2.938 CTBP1 Konstantinos Varvagiannis gene: CTBP1 was added
gene: CTBP1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561
Phenotypes for gene: CTBP1 were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Ataxia; Abnormality of dental enamel
Penetrance for gene: CTBP1 were set to unknown
Mode of pathogenicity for gene: CTBP1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CTBP1 was set to GREEN
gene: CTBP1 was marked as current diagnostic
Added comment: 12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article:
- Beck et al. 2016 (PMID: 27094857) : 4 individuals
- Sommerville et al. 2017 (PMID: 28955726) : 1 subject
- Beck et al. 2019 (PMID: 31041561) : 7 further individuals

Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on.

A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect.

Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism.

Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders).

Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1 ).

Role and Functional studies:
- The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884).
- In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors.
- RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated).
- Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this.
- Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies.

Animal models:
- Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226)
- As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential.

----
CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P.
Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability.
----

As a result, CTBP1 can be added in the current panel probably as green.
Sources: Literature
Hereditary ataxia with onset in adulthood v1.174 VAMP1 Louise Daugherty changed review comment from: Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group


; to: Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Intellectual disability v2.938 TRPM3 Konstantinos Varvagiannis changed review comment from: Dyment et al. (2019 - https://doi.org/10.1038/s41431-019-0462-x) report on 7 unrelated individuals with a recurrent de novo TRPM3 missense variant [NM_020952.4:c.2509G>A - NP_066003.3:p.(Val837Met)] as well as an additional individual with a further de novo missense variant [c.2810C>A or p.(Pro937Gln) - same ref. sequences].

Overlapping features included hypotonia (7/8 - in one case mixed tone abnormality), DD/ID (8/8 - all individuals at appropriate age - degree relevant), EEG-confirmed epilepsy (7/8). Autism-like features were observed in 4 (out of 6 for whom this information was reported). Other features were noted in a minority (or were private to certain) of these individuals.

Different clinical types of seizures were reported incl. absence, generalized-toni-clonic, infantile spasms as well as subclinical ones. Onset was in infancy or early childhood.

In all individuals the variant was found following trio exome sequencing.

The first variant fulfilled ACMG criteria to be classified as pathogenic due to it's de novo occurrence, prevalence in affected individuals (>=6 affected individuals and in the same time) absence from population databases, in silico predictions in favour of pathogenicity (PS2, PS4_Moderate, PM2, PP3).

The Pro937Gln variant is however classified as a VUS. The subject harboring this variant had an additional de novo variant in another gene (DDB1) not associated with any phenotype, to date.

Several other genetic causes had previously been ruled out for most individuals by other investigations : aCGH was normal in all, FMR1 testing in 6 subjects, genes (PHF6, MECP2, MCT8) or smaller panels for ID (the latter in 3 subjects), mtDNA or testing of nuclear genes for mitochondrial disorders, etc.

TRPM3 encodes transient receptor potential (TRP) cation channel, subfamily M, member 3. TRP channels are a superfamily of gated cation channels sensitive to various physical or chemical stimuli (Clapham 2003 - PMID: 14654832 cited) eg. temperature or pain.

The gene is highly expressed in the brain in humans and other vertebrates (Grimm et al. 2003 - PMID : 12672799 and GTEx - https://gtexportal.org/home/gene/TRPM3).

Animal models : In rat brain, expression is initially restricted to neurons but later - as myelination progresses - shifts to oligodendrocytes (cited : Hoffmann et al. 2010 - PMID: 20163522). Most subjects had normal brain MRI appart from one individual with nonspecific white matter hyperintensities and another with possible mild cerebral volume loss. Trpm3 -/- mice show attenuated nocifensive behavior after heat or dermal injection of pregnenolone sulfate. Heat or pain insensitivity was reported only for 2 individuals.

Functional studies were not carried out, although some hypotheses are proposed following in silico modeling of the TRPM3 variants using an available structure for TRPM7.

As discussed by Dyment et al., happloinsufficiency appears to be unlikely given the presence of LoF variants in ExAC/gnomAD (pLI of 0), some intragenic copy number variants in DGV. In addition, pathogenicity of deletions spanning only TRPM3 or additional proximal genes was not evident in 2 cases:
- In the first case a exon 1-9 deletion was found in 2 brothers with Becker muscular dystrophy due to DMD intragenic duplication and autism/cognitive impairment though the TRPM3 deletion was found also in unaffected family members. The deletion was also found in unaffected relatives. A multiple hit hypothesis was hypothesized for this family. [Pagnamenta et al. 2011 - PMID: 21484199]
- Kuniba et al. [2009 - PMID: 19343044] reported a 1.27-Mb deletion spanning TRPM3, KLF9, SMC5 and MAMDC2 in a patient with Kabuki syndrome working diagnosis. Segregation studies were however not possible. At the time, the molecular etiology of Kabuki syndrome (KMT2D/KDM6A) was not known.
-----
TRPM3 is not associated with any phenotype in OMIM or G2P.
This gene is included in panels for ID offered by some diagnostic laboratories (eg. GeneDx participating in the above study).
-----
As a result, TRPM3 seems to fulfill criteria for inclusion in the ID/epilepsy panels probably as green (# of individuals, degree of ID relevant, EEG-confirmed epilepsy) or amber (if further functional evidence would be required).

[Please consider eligibility for inclusion in other possibly relevant panels eg. autism, etc].
Sources: Literature; to: Dyment et al. (2019 - https://doi.org/10.1038/s41431-019-0462-x) report on 7 unrelated individuals with a recurrent de novo TRPM3 missense variant [NM_020952.4:c.2509G>A - NP_066003.3:p.(Val837Met)] as well as an additional individual with a further de novo missense variant [c.2810C>A or p.(Pro937Gln) - same ref. sequences].

Overlapping features included hypotonia (7/8 - in one case mixed tone abnormality), DD/ID (8/8 - all individuals at appropriate age - degree relevant), EEG-confirmed epilepsy (7/8). Autism-like features were observed in 4 (out of 6 for whom this information was reported). Other features were noted in a minority (or were private to certain) of these individuals.

Different clinical types of seizures were reported incl. absence, generalized-toni-clonic, infantile spasms as well as subclinical ones. Onset was in infancy or early childhood.

In all individuals the variant was found following trio exome sequencing.

The first variant fulfilled ACMG criteria to be classified as pathogenic due to it's de novo occurrence, prevalence in affected individuals (>=6 affected individuals and in the same time) absence from population databases, in silico predictions in favour of pathogenicity (PS2, PS4_Moderate, PM2, PP3).

The Pro937Gln variant is however also present once in gnomAD (1/251370 alleles or AF:3.98e-6) and is classified as VUS according to the ACMG criteria. The subject harboring this variant had an additional de novo variant in another gene (DDB1) not associated with any phenotype, to date.

Several other genetic causes had previously been ruled out for most individuals by other investigations : aCGH was normal in all, FMR1 testing in 6 subjects, genes (PHF6, MECP2, MCT8) or smaller panels for ID (the latter in 3 subjects), mtDNA or testing of nuclear genes for mitochondrial disorders, etc.

TRPM3 encodes transient receptor potential (TRP) cation channel, subfamily M, member 3. TRP channels are a superfamily of gated cation channels sensitive to various physical or chemical stimuli (Clapham 2003 - PMID: 14654832 cited) eg. temperature or pain.

The gene is highly expressed in the brain in humans and other vertebrates (Grimm et al. 2003 - PMID : 12672799 and GTEx - https://gtexportal.org/home/gene/TRPM3).

Animal models : In rat brain, expression is initially restricted to neurons but later - as myelination progresses - shifts to oligodendrocytes (cited : Hoffmann et al. 2010 - PMID: 20163522). Most subjects had normal brain MRI appart from one individual with nonspecific white matter hyperintensities and another with possible mild cerebral volume loss. Trpm3 -/- mice show attenuated nocifensive behavior after heat or dermal injection of pregnenolone sulfate. Heat or pain insensitivity was reported only for 2 individuals.

Functional studies were not carried out, although some hypotheses are proposed following in silico modeling of the TRPM3 variants using an available structure for TRPM7.

As discussed by Dyment et al., happloinsufficiency appears to be unlikely given the presence of LoF variants in ExAC/gnomAD (pLI of 0), some intragenic copy number variants in DGV. In addition, pathogenicity of deletions spanning only TRPM3 or additional proximal genes was not evident in 2 cases:
- In the first case a exon 1-9 deletion was found in 2 brothers with Becker muscular dystrophy due to DMD intragenic duplication and autism/cognitive impairment though the TRPM3 deletion was found also in unaffected family members. The deletion was also found in unaffected relatives. A multiple hit hypothesis was hypothesized for this family. [Pagnamenta et al. 2011 - PMID: 21484199]
- Kuniba et al. [2009 - PMID: 19343044] reported a 1.27-Mb deletion spanning TRPM3, KLF9, SMC5 and MAMDC2 in a patient with Kabuki syndrome working diagnosis. Segregation studies were however not possible. At the time, the molecular etiology of Kabuki syndrome (KMT2D/KDM6A) was not known.
-----
TRPM3 is not associated with any phenotype in OMIM or G2P.
This gene is included in panels for ID offered by some diagnostic laboratories (eg. GeneDx participating in the above study).
-----
As a result, TRPM3 seems to fulfill criteria for inclusion in the ID/epilepsy panels probably as green (# of individuals, degree of ID relevant, EEG-confirmed epilepsy) or amber (if further functional evidence would be required).

[Please consider eligibility for inclusion in other possibly relevant panels eg. autism, etc].
Sources: Literature
Early onset or syndromic epilepsy v1.128 TRPM3 Konstantinos Varvagiannis changed review comment from: Dyment et al. (2019 - https://doi.org/10.1038/s41431-019-0462-x) report on 7 unrelated individuals with a recurrent de novo TRPM3 missense variant [NM_020952.4:c.2509G>A - NP_066003.3:p.(Val837Met)] as well as an additional individual with a further de novo missense variant [c.2810C>A or p.(Pro937Gln) - same ref. sequences].

Overlapping features included hypotonia (7/8 - in one case mixed tone abnormality), DD/ID (8/8 - all individuals at appropriate age - degree relevant), EEG-confirmed epilepsy (7/8). Autism-like features were observed in 4 (out of 6 for whom this information was reported). Other features were noted in a minority (or were private to certain) of these individuals.

Different clinical types of seizures were reported incl. absence, generalized-toni-clonic, infantile spasms as well as subclinical ones. Onset was in infancy or early childhood.

In all individuals the variant was found following trio exome sequencing.

The first variant fulfilled ACMG criteria to be classified as pathogenic due to it's de novo occurrence, prevalence in affected individuals (>=6 affected individuals and in the same time) absence from population databases, in silico predictions in favour of pathogenicity (PS2, PS4_Moderate, PM2, PP3).

The Pro937Gln variant is however classified as a VUS. The subject harboring this variant had an additional de novo variant in another gene (DDB1) not associated with any phenotype, to date.

Several other genetic causes had previously been ruled out for most individuals by other investigations : aCGH was normal in all, FMR1 testing in 6 subjects, genes (PHF6, MECP2, MCT8) or smaller panels for ID (the latter in 3 subjects), mtDNA or testing of nuclear genes for mitochondrial disorders, etc.

TRPM3 encodes transient receptor potential (TRP) cation channel, subfamily M, member 3. TRP channels are a superfamily of gated cation channels sensitive to various physical or chemical stimuli (Clapham 2003 - PMID: 14654832 cited) eg. temperature or pain.

The gene is highly expressed in the brain in humans and other vertebrates (Grimm et al. 2003 - PMID : 12672799 and GTEx - https://gtexportal.org/home/gene/TRPM3).

Animal models : In rat brain, expression is initially restricted to neurons but later - as myelination progresses - shifts to oligodendrocytes (cited : Hoffmann et al. 2010 - PMID: 20163522). Most subjects had normal brain MRI appart from one individual with nonspecific white matter hyperintensities and another with possible mild cerebral volume loss. Trpm3 -/- mice show attenuated nocifensive behavior after heat or dermal injection of pregnenolone sulfate. Heat or pain insensitivity was reported only for 2 individuals.

Functional studies were not carried out, although some hypotheses are proposed following in silico modeling of the TRPM3 variants using an available structure for TRPM7.

As discussed by Dyment et al., happloinsufficiency appears to be unlikely given the presence of LoF variants in ExAC/gnomAD (pLI of 0), some intragenic copy number variants in DGV. In addition, pathogenicity of deletions spanning only TRPM3 or additional proximal genes was not evident in 2 cases:
- In the first case a exon 1-9 deletion was found in 2 brothers with Becker muscular dystrophy due to DMD intragenic duplication and autism/cognitive impairment though the TRPM3 deletion was found also in unaffected family members. The deletion was also found in unaffected relatives. A multiple hit hypothesis was hypothesized for this family. [Pagnamenta et al. 2011 - PMID: 21484199]
- Kuniba et al. [2009 - PMID: 19343044] reported a 1.27-Mb deletion spanning TRPM3, KLF9, SMC5 and MAMDC2 in a patient with Kabuki syndrome working diagnosis. Segregation studies were however not possible. At the time, the molecular etiology of Kabuki syndrome (KMT2D/KDM6A) was not known.
-----
TRPM3 is not associated with any phenotype in OMIM or G2P.
This gene is included in panels for ID offered by some diagnostic laboratories (eg. GeneDx participating in the above study).
-----
As a result, TRPM3 seems to fulfill criteria for inclusion in the ID/epilepsy panels probably as green (# of individuals, degree of ID relevant, EEG-confirmed epilepsy) or amber (if further functional evidence would be required).

[Please consider eligibility for inclusion in other possibly relevant panels eg. autism, etc].
Sources: Literature; to: Dyment et al. (2019 - https://doi.org/10.1038/s41431-019-0462-x) report on 7 unrelated individuals with a recurrent de novo TRPM3 missense variant [NM_020952.4:c.2509G>A - NP_066003.3:p.(Val837Met)] as well as an additional individual with a further de novo missense variant [c.2810C>A or p.(Pro937Gln) - same ref. sequences].

Overlapping features included hypotonia (7/8 - in one case mixed tone abnormality), DD/ID (8/8 - all individuals at appropriate age - degree relevant), EEG-confirmed epilepsy (7/8). Autism-like features were observed in 4 (out of 6 for whom this information was reported). Other features were noted in a minority (or were private to certain) of these individuals.

Different clinical types of seizures were reported incl. absence, generalized-toni-clonic, infantile spasms as well as subclinical ones. Onset was in infancy or early childhood.

In all individuals the variant was found following trio exome sequencing.

The first variant fulfilled ACMG criteria to be classified as pathogenic due to it's de novo occurrence, prevalence in affected individuals (>=6 affected individuals and in the same time) absence from population databases, in silico predictions in favour of pathogenicity (PS2, PS4_Moderate, PM2, PP3).

The Pro937Gln variant is however also present once in gnomAD (1/251370 alleles or AF:3.98e-6) and is classified as VUS according to the ACMG criteria. The subject harboring this variant had an additional de novo variant in another gene (DDB1) not associated with any phenotype, to date.

Several other genetic causes had previously been ruled out for most individuals by other investigations : aCGH was normal in all, FMR1 testing in 6 subjects, genes (PHF6, MECP2, MCT8) or smaller panels for ID (the latter in 3 subjects), mtDNA or testing of nuclear genes for mitochondrial disorders, etc.

TRPM3 encodes transient receptor potential (TRP) cation channel, subfamily M, member 3. TRP channels are a superfamily of gated cation channels sensitive to various physical or chemical stimuli (Clapham 2003 - PMID: 14654832 cited) eg. temperature or pain.

The gene is highly expressed in the brain in humans and other vertebrates (Grimm et al. 2003 - PMID : 12672799 and GTEx - https://gtexportal.org/home/gene/TRPM3).

Animal models : In rat brain, expression is initially restricted to neurons but later - as myelination progresses - shifts to oligodendrocytes (cited : Hoffmann et al. 2010 - PMID: 20163522). Most subjects had normal brain MRI appart from one individual with nonspecific white matter hyperintensities and another with possible mild cerebral volume loss. Trpm3 -/- mice show attenuated nocifensive behavior after heat or dermal injection of pregnenolone sulfate. Heat or pain insensitivity was reported only for 2 individuals.

Functional studies were not carried out, although some hypotheses are proposed following in silico modeling of the TRPM3 variants using an available structure for TRPM7.

As discussed by Dyment et al., happloinsufficiency appears to be unlikely given the presence of LoF variants in ExAC/gnomAD (pLI of 0), some intragenic copy number variants in DGV. In addition, pathogenicity of deletions spanning only TRPM3 or additional proximal genes was not evident in 2 cases:
- In the first case a exon 1-9 deletion was found in 2 brothers with Becker muscular dystrophy due to DMD intragenic duplication and autism/cognitive impairment though the TRPM3 deletion was found also in unaffected family members. The deletion was also found in unaffected relatives. A multiple hit hypothesis was hypothesized for this family. [Pagnamenta et al. 2011 - PMID: 21484199]
- Kuniba et al. [2009 - PMID: 19343044] reported a 1.27-Mb deletion spanning TRPM3, KLF9, SMC5 and MAMDC2 in a patient with Kabuki syndrome working diagnosis. Segregation studies were however not possible. At the time, the molecular etiology of Kabuki syndrome (KMT2D/KDM6A) was not known.
-----
TRPM3 is not associated with any phenotype in OMIM or G2P.
This gene is included in panels for ID offered by some diagnostic laboratories (eg. GeneDx participating in the above study).
-----
As a result, TRPM3 seems to fulfill criteria for inclusion in the ID/epilepsy panels probably as green (# of individuals, degree of ID relevant, EEG-confirmed epilepsy) or amber (if further functional evidence would be required).

[Please consider eligibility for inclusion in other possibly relevant panels eg. autism, etc].
Sources: Literature
Early onset or syndromic epilepsy v1.128 TRPM3 Konstantinos Varvagiannis gene: TRPM3 was added
gene: TRPM3 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRPM3 were set to doi.org/10.1038/s41431-019-0462-x
Phenotypes for gene: TRPM3 were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior
Penetrance for gene: TRPM3 were set to unknown
Mode of pathogenicity for gene: TRPM3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: TRPM3 was set to GREEN
Added comment: Dyment et al. (2019 - https://doi.org/10.1038/s41431-019-0462-x) report on 7 unrelated individuals with a recurrent de novo TRPM3 missense variant [NM_020952.4:c.2509G>A - NP_066003.3:p.(Val837Met)] as well as an additional individual with a further de novo missense variant [c.2810C>A or p.(Pro937Gln) - same ref. sequences].

Overlapping features included hypotonia (7/8 - in one case mixed tone abnormality), DD/ID (8/8 - all individuals at appropriate age - degree relevant), EEG-confirmed epilepsy (7/8). Autism-like features were observed in 4 (out of 6 for whom this information was reported). Other features were noted in a minority (or were private to certain) of these individuals.

Different clinical types of seizures were reported incl. absence, generalized-toni-clonic, infantile spasms as well as subclinical ones. Onset was in infancy or early childhood.

In all individuals the variant was found following trio exome sequencing.

The first variant fulfilled ACMG criteria to be classified as pathogenic due to it's de novo occurrence, prevalence in affected individuals (>=6 affected individuals and in the same time) absence from population databases, in silico predictions in favour of pathogenicity (PS2, PS4_Moderate, PM2, PP3).

The Pro937Gln variant is however classified as a VUS. The subject harboring this variant had an additional de novo variant in another gene (DDB1) not associated with any phenotype, to date.

Several other genetic causes had previously been ruled out for most individuals by other investigations : aCGH was normal in all, FMR1 testing in 6 subjects, genes (PHF6, MECP2, MCT8) or smaller panels for ID (the latter in 3 subjects), mtDNA or testing of nuclear genes for mitochondrial disorders, etc.

TRPM3 encodes transient receptor potential (TRP) cation channel, subfamily M, member 3. TRP channels are a superfamily of gated cation channels sensitive to various physical or chemical stimuli (Clapham 2003 - PMID: 14654832 cited) eg. temperature or pain.

The gene is highly expressed in the brain in humans and other vertebrates (Grimm et al. 2003 - PMID : 12672799 and GTEx - https://gtexportal.org/home/gene/TRPM3).

Animal models : In rat brain, expression is initially restricted to neurons but later - as myelination progresses - shifts to oligodendrocytes (cited : Hoffmann et al. 2010 - PMID: 20163522). Most subjects had normal brain MRI appart from one individual with nonspecific white matter hyperintensities and another with possible mild cerebral volume loss. Trpm3 -/- mice show attenuated nocifensive behavior after heat or dermal injection of pregnenolone sulfate. Heat or pain insensitivity was reported only for 2 individuals.

Functional studies were not carried out, although some hypotheses are proposed following in silico modeling of the TRPM3 variants using an available structure for TRPM7.

As discussed by Dyment et al., happloinsufficiency appears to be unlikely given the presence of LoF variants in ExAC/gnomAD (pLI of 0), some intragenic copy number variants in DGV. In addition, pathogenicity of deletions spanning only TRPM3 or additional proximal genes was not evident in 2 cases:
- In the first case a exon 1-9 deletion was found in 2 brothers with Becker muscular dystrophy due to DMD intragenic duplication and autism/cognitive impairment though the TRPM3 deletion was found also in unaffected family members. The deletion was also found in unaffected relatives. A multiple hit hypothesis was hypothesized for this family. [Pagnamenta et al. 2011 - PMID: 21484199]
- Kuniba et al. [2009 - PMID: 19343044] reported a 1.27-Mb deletion spanning TRPM3, KLF9, SMC5 and MAMDC2 in a patient with Kabuki syndrome working diagnosis. Segregation studies were however not possible. At the time, the molecular etiology of Kabuki syndrome (KMT2D/KDM6A) was not known.
-----
TRPM3 is not associated with any phenotype in OMIM or G2P.
This gene is included in panels for ID offered by some diagnostic laboratories (eg. GeneDx participating in the above study).
-----
As a result, TRPM3 seems to fulfill criteria for inclusion in the ID/epilepsy panels probably as green (# of individuals, degree of ID relevant, EEG-confirmed epilepsy) or amber (if further functional evidence would be required).

[Please consider eligibility for inclusion in other possibly relevant panels eg. autism, etc].
Sources: Literature
Intellectual disability v2.938 TRPM3 Konstantinos Varvagiannis gene: TRPM3 was added
gene: TRPM3 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRPM3 were set to doi.org/10.1038/s41431-019-0462-x
Phenotypes for gene: TRPM3 were set to Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior
Penetrance for gene: TRPM3 were set to unknown
Mode of pathogenicity for gene: TRPM3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: TRPM3 was set to GREEN
gene: TRPM3 was marked as current diagnostic
Added comment: Dyment et al. (2019 - https://doi.org/10.1038/s41431-019-0462-x) report on 7 unrelated individuals with a recurrent de novo TRPM3 missense variant [NM_020952.4:c.2509G>A - NP_066003.3:p.(Val837Met)] as well as an additional individual with a further de novo missense variant [c.2810C>A or p.(Pro937Gln) - same ref. sequences].

Overlapping features included hypotonia (7/8 - in one case mixed tone abnormality), DD/ID (8/8 - all individuals at appropriate age - degree relevant), EEG-confirmed epilepsy (7/8). Autism-like features were observed in 4 (out of 6 for whom this information was reported). Other features were noted in a minority (or were private to certain) of these individuals.

Different clinical types of seizures were reported incl. absence, generalized-toni-clonic, infantile spasms as well as subclinical ones. Onset was in infancy or early childhood.

In all individuals the variant was found following trio exome sequencing.

The first variant fulfilled ACMG criteria to be classified as pathogenic due to it's de novo occurrence, prevalence in affected individuals (>=6 affected individuals and in the same time) absence from population databases, in silico predictions in favour of pathogenicity (PS2, PS4_Moderate, PM2, PP3).

The Pro937Gln variant is however classified as a VUS. The subject harboring this variant had an additional de novo variant in another gene (DDB1) not associated with any phenotype, to date.

Several other genetic causes had previously been ruled out for most individuals by other investigations : aCGH was normal in all, FMR1 testing in 6 subjects, genes (PHF6, MECP2, MCT8) or smaller panels for ID (the latter in 3 subjects), mtDNA or testing of nuclear genes for mitochondrial disorders, etc.

TRPM3 encodes transient receptor potential (TRP) cation channel, subfamily M, member 3. TRP channels are a superfamily of gated cation channels sensitive to various physical or chemical stimuli (Clapham 2003 - PMID: 14654832 cited) eg. temperature or pain.

The gene is highly expressed in the brain in humans and other vertebrates (Grimm et al. 2003 - PMID : 12672799 and GTEx - https://gtexportal.org/home/gene/TRPM3).

Animal models : In rat brain, expression is initially restricted to neurons but later - as myelination progresses - shifts to oligodendrocytes (cited : Hoffmann et al. 2010 - PMID: 20163522). Most subjects had normal brain MRI appart from one individual with nonspecific white matter hyperintensities and another with possible mild cerebral volume loss. Trpm3 -/- mice show attenuated nocifensive behavior after heat or dermal injection of pregnenolone sulfate. Heat or pain insensitivity was reported only for 2 individuals.

Functional studies were not carried out, although some hypotheses are proposed following in silico modeling of the TRPM3 variants using an available structure for TRPM7.

As discussed by Dyment et al., happloinsufficiency appears to be unlikely given the presence of LoF variants in ExAC/gnomAD (pLI of 0), some intragenic copy number variants in DGV. In addition, pathogenicity of deletions spanning only TRPM3 or additional proximal genes was not evident in 2 cases:
- In the first case a exon 1-9 deletion was found in 2 brothers with Becker muscular dystrophy due to DMD intragenic duplication and autism/cognitive impairment though the TRPM3 deletion was found also in unaffected family members. The deletion was also found in unaffected relatives. A multiple hit hypothesis was hypothesized for this family. [Pagnamenta et al. 2011 - PMID: 21484199]
- Kuniba et al. [2009 - PMID: 19343044] reported a 1.27-Mb deletion spanning TRPM3, KLF9, SMC5 and MAMDC2 in a patient with Kabuki syndrome working diagnosis. Segregation studies were however not possible. At the time, the molecular etiology of Kabuki syndrome (KMT2D/KDM6A) was not known.
-----
TRPM3 is not associated with any phenotype in OMIM or G2P.
This gene is included in panels for ID offered by some diagnostic laboratories (eg. GeneDx participating in the above study).
-----
As a result, TRPM3 seems to fulfill criteria for inclusion in the ID/epilepsy panels probably as green (# of individuals, degree of ID relevant, EEG-confirmed epilepsy) or amber (if further functional evidence would be required).

[Please consider eligibility for inclusion in other possibly relevant panels eg. autism, etc].
Sources: Literature
Lipodystrophy - childhood onset v1.7 CAV1 Ivone Leong Classified gene: CAV1 as Green List (high evidence)
Lipodystrophy - childhood onset v1.7 CAV1 Ivone Leong Added comment: Comment on list classification: New gene added by reviewer. After reviewing the evidence provided by the expert reviewer, it was decided that there is enough evidence to promote this gene from amber to green.

It should be noted that causative variants might only be those that are either homozygous null variants or heterozygous variants that causes truncated protein to be made.
Lipodystrophy - childhood onset v1.7 CAV1 Ivone Leong Gene: cav1 has been classified as Green List (High Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v0.150 C11orf70 Louise Daugherty Publications for gene: C11orf70 were set to
Lipodystrophy - childhood onset v1.6 CAV1 Kevin Colclough commented on gene: CAV1: Id initially classified as green but I think this is more complex due to the fact that there are reports of both dominant and recessively inherited variants causing different phenotypes.I think there is a genotype-phenotype association here, and I dont think haploinsufficiency is a disease mechanism since individuals with heterozygous loss of protein expression do not have a lipodystrophy phenotype (whole gene deletion patients and the heterozygous parents with p.Glu38Ter).All other reported variants are within the last exon and are expected to escape nonsense mediated decay, generating a truncated protein or a full length protein with an altered C-terminal sequence. The p.(Phe160Ter) variant looks to be a definite CGL causing variant. Then there are two other PTC variants resulting in a shorter protein with a lipodystrophy phenotype. And finally two patients with very similar frameshift variants that result in full-length proteins with altered C-terminal amino acid sequence. So it could be that only homozygous null variants or heterozygous variants that result in a truncated protein are causing a lipodystrophy phenotype.
Lipodystrophy - childhood onset v1.5 CAV1 Ivone Leong Phenotypes for gene: CAV1 were changed from ?Lipodystrophy, congenital generalized, type 3, 612526 to ?Lipodystrophy, congenital generalized, type 3, 612526; Lipodystrophy, familial partial, type 7, 606721
Undiagnosed metabolic disorders v1.118 FUT8 Louise Daugherty Classified gene: FUT8 as Green List (high evidence)
Undiagnosed metabolic disorders v1.118 FUT8 Louise Daugherty Gene: fut8 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.128 FUT8 Louise Daugherty Phenotypes for gene: FUT8 were changed from Congenital disorder of glycosylation with defective fucosylation, 618005; Intellectual disability to Congenital disorder of glycosylation with defective fucosylation, 618005; seizures
Early onset or syndromic epilepsy v1.127 FUT8 Louise Daugherty Deleted their comment
Undiagnosed metabolic disorders v1.117 FUT8 Louise Daugherty gene: FUT8 was added
gene: FUT8 was added to Undiagnosed metabolic disorders. Sources: Expert Review
Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT8 were set to 29304374
Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation, 618005
Review for gene: FUT8 was set to GREEN
Added comment: Adding to Undiagnosed metabolic disorders panel after reviewing panels for GMS, as recommended by the Genomics England clinical team, to benefit the 100K participants. Enough evidence to support gene-disease association and relevance to this panel to rate this gene Green.
Sources: Expert Review
Fetal anomalies v0.296 PDHB Anna de Burca gene: PDHB was added
gene: PDHB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHB were set to 26865159
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency
Review for gene: PDHB was set to AMBER
Added comment: PMID:26865159 reports a fetus with homozygous variants in PDHB where there was antenatal presentation of pyruvate dehydrogenase deficiency associated with craniofacial features and structural neurological defects.
Sources: Literature
Fetal anomalies v0.295 PDHA1 Anna de Burca reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26865159; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset leukodystrophy v0.10 ZFYVE26 Louise Daugherty reviewed gene: ZFYVE26: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 TYROBP Louise Daugherty reviewed gene: TYROBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 TUBB4A Louise Daugherty reviewed gene: TUBB4A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 TREX1 Louise Daugherty reviewed gene: TREX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 TREM2 Louise Daugherty reviewed gene: TREM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 SPG11 Louise Daugherty reviewed gene: SPG11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 SAMHD1 Louise Daugherty reviewed gene: SAMHD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 RPS6KA3 Louise Daugherty reviewed gene: RPS6KA3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 RNF216 Louise Daugherty reviewed gene: RNF216: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 RNASET2 Louise Daugherty reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 RNASEH2C Louise Daugherty reviewed gene: RNASEH2C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 RNASEH2B Louise Daugherty reviewed gene: RNASEH2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 RNASEH2A Louise Daugherty reviewed gene: RNASEH2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PTEN Louise Daugherty reviewed gene: PTEN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PSAP Louise Daugherty reviewed gene: PSAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 POLR3B Louise Daugherty reviewed gene: POLR3B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 POLR3A Louise Daugherty reviewed gene: POLR3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 POLR1C Louise Daugherty reviewed gene: POLR1C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PLP1 Louise Daugherty reviewed gene: PLP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX7 Louise Daugherty reviewed gene: PEX7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX6 Louise Daugherty reviewed gene: PEX6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX5 Louise Daugherty reviewed gene: PEX5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX3 Louise Daugherty reviewed gene: PEX3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX26 Louise Daugherty reviewed gene: PEX26: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX2 Louise Daugherty reviewed gene: PEX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX19 Louise Daugherty reviewed gene: PEX19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX16 Louise Daugherty reviewed gene: PEX16: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX14 Louise Daugherty reviewed gene: PEX14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX13 Louise Daugherty reviewed gene: PEX13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX12 Louise Daugherty reviewed gene: PEX12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX11B Louise Daugherty reviewed gene: PEX11B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX10 Louise Daugherty reviewed gene: PEX10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PEX1 Louise Daugherty reviewed gene: PEX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 PAH Louise Daugherty reviewed gene: PAH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 OCRL Louise Daugherty reviewed gene: OCRL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 NOTCH3 Louise Daugherty reviewed gene: NOTCH3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 MTHFR Louise Daugherty reviewed gene: MTHFR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 MCOLN1 Louise Daugherty reviewed gene: MCOLN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 MARS Louise Daugherty reviewed gene: MARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 LMNB1 Louise Daugherty reviewed gene: LMNB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 L2HGDH Louise Daugherty reviewed gene: L2HGDH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 KIF5A Louise Daugherty reviewed gene: KIF5A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 HTRA1 Louise Daugherty reviewed gene: HTRA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 HMGCL Louise Daugherty reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 HEXA Louise Daugherty reviewed gene: HEXA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 HEPACAM Louise Daugherty reviewed gene: HEPACAM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GLB1 Louise Daugherty reviewed gene: GLB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GLA Louise Daugherty reviewed gene: GLA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GJC2 Louise Daugherty reviewed gene: GJC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GJB1 Louise Daugherty reviewed gene: GJB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GJA1 Louise Daugherty reviewed gene: GJA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GFAP Louise Daugherty reviewed gene: GFAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GBE1 Louise Daugherty reviewed gene: GBE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 GALC Louise Daugherty reviewed gene: GALC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 EIF2B5 Louise Daugherty reviewed gene: EIF2B5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 EIF2B4 Louise Daugherty reviewed gene: EIF2B4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 EIF2B3 Louise Daugherty reviewed gene: EIF2B3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 EIF2B2 Louise Daugherty reviewed gene: EIF2B2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 EIF2B1 Louise Daugherty reviewed gene: EIF2B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 EARS2 Louise Daugherty reviewed gene: EARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 DARS2 Louise Daugherty reviewed gene: DARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 DARS Louise Daugherty reviewed gene: DARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 CYP27A1 Louise Daugherty reviewed gene: CYP27A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 CTSA Louise Daugherty reviewed gene: CTSA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 CTC1 Louise Daugherty reviewed gene: CTC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 CSF1R Louise Daugherty reviewed gene: CSF1R: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 COL4A2 Louise Daugherty reviewed gene: COL4A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 COL4A1 Louise Daugherty reviewed gene: COL4A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 CLCN2 Louise Daugherty reviewed gene: CLCN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 ARSA Louise Daugherty reviewed gene: ARSA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 ALDH3A2 Louise Daugherty reviewed gene: ALDH3A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 ADAR Louise Daugherty reviewed gene: ADAR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 ABCD1 Louise Daugherty reviewed gene: ABCD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 AARS2 Louise Daugherty reviewed gene: AARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v0.10 AARS Louise Daugherty reviewed gene: AARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Familial chylomicronaemia syndrome (FCS) v0.8 LIPI Sarah Leigh Classified gene: LIPI as Red List (low evidence)
Familial chylomicronaemia syndrome (FCS) v0.8 LIPI Sarah Leigh Added comment: Comment on list classification: The gene / disease association has been recently been revoked on OMIM as the reported variant (rs11909217) is present in 1,382 of 282,752 alleles and in 8 homozygotes in the gnomAD database (Personal communication to OMIM by Ada Hamosh June 25, 2019).
Familial chylomicronaemia syndrome (FCS) v0.8 LIPI Sarah Leigh Gene: lipi has been classified as Red List (Low Evidence).
Adult onset leukodystrophy v0.9 ZFYVE26 Ian Berry reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 TYROBP Ian Berry reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 TUBB4A Ian Berry reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 TREX1 Ian Berry reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 TREM2 Ian Berry reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 SPG11 Ian Berry reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 SAMHD1 Ian Berry reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 RPS6KA3 Ian Berry reviewed gene: RPS6KA3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 RNF216 Ian Berry reviewed gene: RNF216: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 RNASET2 Ian Berry reviewed gene: RNASET2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 RNASEH2C Ian Berry reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 RNASEH2B Ian Berry reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 RNASEH2A Ian Berry reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PTEN Ian Berry reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PSAP Ian Berry reviewed gene: PSAP: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 POLR3B Ian Berry reviewed gene: POLR3B: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 POLR3A Ian Berry reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 POLR1C Ian Berry reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PLP1 Ian Berry reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX7 Ian Berry reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX6 Ian Berry reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX5 Ian Berry reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX3 Ian Berry reviewed gene: PEX3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX26 Ian Berry reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX2 Ian Berry reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX19 Ian Berry reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX16 Ian Berry reviewed gene: PEX16: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX14 Ian Berry reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX13 Ian Berry reviewed gene: PEX13: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX12 Ian Berry reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX11B Ian Berry reviewed gene: PEX11B: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX10 Ian Berry reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PEX1 Ian Berry reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 PAH Ian Berry reviewed gene: PAH: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 OCRL Ian Berry reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 NOTCH3 Ian Berry reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 MTHFR Ian Berry reviewed gene: MTHFR: Rating: GREEN; Mode of pathogenicity: ; Publications: 29391032; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 MCOLN1 Ian Berry reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 MARS Ian Berry reviewed gene: MARS: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 LMNB1 Ian Berry reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 L2HGDH Ian Berry reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 KIF5A Ian Berry reviewed gene: KIF5A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 HTRA1 Ian Berry reviewed gene: HTRA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 HMGCL Ian Berry reviewed gene: HMGCL: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 HEXA Ian Berry reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 HEPACAM Ian Berry reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GLB1 Ian Berry reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GLA Ian Berry reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GJC2 Ian Berry reviewed gene: GJC2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GJB1 Ian Berry reviewed gene: GJB1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GJA1 Ian Berry reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GFAP Ian Berry reviewed gene: GFAP: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GBE1 Ian Berry reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 GALC Ian Berry reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 EIF2B5 Ian Berry reviewed gene: EIF2B5: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 EIF2B4 Ian Berry reviewed gene: EIF2B4: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 EIF2B3 Ian Berry reviewed gene: EIF2B3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 EIF2B2 Ian Berry reviewed gene: EIF2B2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 EIF2B1 Ian Berry reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 EARS2 Ian Berry reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 DARS2 Ian Berry reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 DARS Ian Berry reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 CYP27A1 Ian Berry reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 CTSA Ian Berry reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 CTC1 Ian Berry reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 CSF1R Ian Berry reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 COL4A2 Ian Berry reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 COL4A1 Ian Berry reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 CLCN2 Ian Berry reviewed gene: CLCN2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 ARSA Ian Berry reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 ALDH3A2 Ian Berry reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 ADAR Ian Berry reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 ABCD1 Ian Berry reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 AARS2 Ian Berry reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset leukodystrophy v0.9 AARS Ian Berry reviewed gene: AARS: Rating: GREEN; Mode of pathogenicity: ; Publications: 28334938, 25527826, 27159321, 24357685, 20301621; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.7 LIPI Sarah Leigh Classified gene: LIPI as Red List (low evidence)
Familial chylomicronaemia syndrome (FCS) v0.7 LIPI Sarah Leigh Gene: lipi has been classified as Red List (Low Evidence).
Familial chylomicronaemia syndrome (FCS) v0.6 LPL Maggie Williams reviewed gene: LPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 LMF1 Maggie Williams reviewed gene: LMF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 LIPI Maggie Williams reviewed gene: LIPI: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 GPIHBP1 Maggie Williams reviewed gene: GPIHBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 GPD1 Maggie Williams reviewed gene: GPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 CREB3L3 Maggie Williams reviewed gene: CREB3L3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 APOE Maggie Williams reviewed gene: APOE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 APOC2 Maggie Williams reviewed gene: APOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 APOB Maggie Williams reviewed gene: APOB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.6 APOA5 Maggie Williams reviewed gene: APOA5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Familial chylomicronaemia syndrome (FCS) v0.5 CREB3L3 Sarah Leigh Publications for gene: CREB3L3 were set to 29954705; 21666694; 26427795
Early onset or syndromic epilepsy v1.127 PEX5 Rebecca Foulger commented on gene: PEX5
Familial chylomicronaemia syndrome (FCS) v0.4 LMF1 Sarah Leigh Publications for gene: LMF1 were set to 30885219
Familial chylomicronaemia syndrome (FCS) v0.3 LMF1 Sarah Leigh commented on gene: LMF1
Early onset or syndromic epilepsy v1.127 HEXB Rebecca Foulger Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures to Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures; myoclonic epilepsy
Early onset or syndromic epilepsy v1.126 HEXB Rebecca Foulger Publications for gene: HEXB were set to 2967418; 21153386; 22848519; 30075786
Early onset or syndromic epilepsy v1.125 HEXB Rebecca Foulger commented on gene: HEXB: PMID:28553389: Gowda et al., 2017 report a 1 year old boy with Sanhoff disease without hepatosplenomegaly, and a homozygous missense variant in HEXB (p.Cys534Tyr). The boy suffered from focal seizures from 11 months. A sibling died age 18 months with 'similar complaints'. Further controls or segregation analysis was not performed. The authors say the same variant was reported previously in a Japanese case which showed myoclonic epilepsy and hepatosplenomegaly (PMID:7626071).
Early onset or syndromic epilepsy v1.125 HEXB Rebecca Foulger Publications for gene: HEXB were set to 2967418; 21153386; 22848519
Early onset or syndromic epilepsy v1.124 HEXB Rebecca Foulger commented on gene: HEXB: PMID: 30075786: Tavasoli et al., 2018 studied 25 Iranian patients with Sandhoff disease. 8/25 patients had seizures (Table 2) with a mean age at presentation 5.6 months. HEXB gene mutation studies were performed in 8 patients, including 2 patients with seizures (novel HEXB variants were identified in patients 4 and 13).
Early onset or syndromic epilepsy v1.124 HEXB Rebecca Foulger commented on gene: HEXB
Early onset or syndromic epilepsy v1.124 HEXB Rebecca Foulger Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, 268800; seizures
Early onset or syndromic epilepsy v1.123 HEXB Rebecca Foulger Publications for gene: HEXB were set to 2967418; 21153386
Adult onset leukodystrophy v0.8 ZFYVE26 Louise Daugherty Publications for gene ZFYVE26 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 TYROBP Louise Daugherty Publications for gene TYROBP were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 TUBB4A Louise Daugherty Publications for gene TUBB4A were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 TREX1 Louise Daugherty Publications for gene TREX1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 TREM2 Louise Daugherty Publications for gene TREM2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 SPG11 Louise Daugherty Publications for gene SPG11 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 SAMHD1 Louise Daugherty Publications for gene SAMHD1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 RPS6KA3 Louise Daugherty Publications for gene RPS6KA3 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 RNF216 Louise Daugherty Publications for gene RNF216 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 RNASET2 Louise Daugherty Publications for gene RNASET2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 RNASEH2C Louise Daugherty Publications for gene RNASEH2C were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 RNASEH2B Louise Daugherty Publications for gene RNASEH2B were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 RNASEH2A Louise Daugherty Publications for gene RNASEH2A were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PTEN Louise Daugherty Publications for gene PTEN were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PSAP Louise Daugherty Publications for gene PSAP were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 POLR3B Louise Daugherty Publications for gene POLR3B were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 POLR3A Louise Daugherty Publications for gene POLR3A were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 POLR1C Louise Daugherty Publications for gene POLR1C were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PLP1 Louise Daugherty Publications for gene PLP1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX7 Louise Daugherty Publications for gene PEX7 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX6 Louise Daugherty Publications for gene PEX6 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX5 Louise Daugherty Publications for gene PEX5 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX3 Louise Daugherty Publications for gene PEX3 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX26 Louise Daugherty Publications for gene PEX26 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX2 Louise Daugherty Publications for gene PEX2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX19 Louise Daugherty Publications for gene PEX19 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX16 Louise Daugherty Publications for gene PEX16 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX14 Louise Daugherty Publications for gene PEX14 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX13 Louise Daugherty Publications for gene PEX13 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX12 Louise Daugherty Publications for gene PEX12 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX11B Louise Daugherty Publications for gene PEX11B were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX10 Louise Daugherty Publications for gene PEX10 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PEX1 Louise Daugherty Publications for gene PEX1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 PAH Louise Daugherty Publications for gene PAH were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 OCRL Louise Daugherty Publications for gene OCRL were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 NOTCH3 Louise Daugherty Publications for gene NOTCH3 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 MTHFR Louise Daugherty Publications for gene MTHFR were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 MCOLN1 Louise Daugherty Publications for gene MCOLN1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 MARS Louise Daugherty Publications for gene MARS were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 LMNB1 Louise Daugherty Publications for gene LMNB1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 L2HGDH Louise Daugherty Publications for gene L2HGDH were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 KIF5A Louise Daugherty Publications for gene KIF5A were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 HTRA1 Louise Daugherty Publications for gene HTRA1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 HMGCL Louise Daugherty Publications for gene HMGCL were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 HEXA Louise Daugherty Publications for gene HEXA were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 HEPACAM Louise Daugherty Publications for gene HEPACAM were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GLB1 Louise Daugherty Publications for gene GLB1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GLA Louise Daugherty Publications for gene GLA were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GJC2 Louise Daugherty Publications for gene GJC2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GJB1 Louise Daugherty Publications for gene GJB1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GJA1 Louise Daugherty Publications for gene GJA1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GFAP Louise Daugherty Publications for gene GFAP were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GBE1 Louise Daugherty Publications for gene GBE1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 GALC Louise Daugherty Publications for gene GALC were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 EIF2B5 Louise Daugherty Publications for gene EIF2B5 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 EIF2B4 Louise Daugherty Publications for gene EIF2B4 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 EIF2B3 Louise Daugherty Publications for gene EIF2B3 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 EIF2B2 Louise Daugherty Publications for gene EIF2B2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 EIF2B1 Louise Daugherty Publications for gene EIF2B1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 EARS2 Louise Daugherty Publications for gene EARS2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 DARS2 Louise Daugherty Publications for gene DARS2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 DARS Louise Daugherty Publications for gene DARS were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 CYP27A1 Louise Daugherty Publications for gene CYP27A1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 CTSA Louise Daugherty Publications for gene CTSA were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 CTC1 Louise Daugherty Publications for gene CTC1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 CSF1R Louise Daugherty Publications for gene CSF1R were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 COL4A2 Louise Daugherty Publications for gene COL4A2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 COL4A1 Louise Daugherty Publications for gene COL4A1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 CLCN2 Louise Daugherty Publications for gene CLCN2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 ARSA Louise Daugherty Publications for gene ARSA were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 ALDH3A2 Louise Daugherty Publications for gene ALDH3A2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 ADAR Louise Daugherty Publications for gene ADAR were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 ABCD1 Louise Daugherty Publications for gene ABCD1 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 AARS2 Louise Daugherty Publications for gene AARS2 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v0.8 AARS Louise Daugherty Publications for gene AARS were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Familial chylomicronaemia syndrome (FCS) v0.3 LMF1 Sarah Leigh Publications for gene: LMF1 were set to
Early onset or syndromic epilepsy v1.122 DPM2 Rebecca Foulger Phenotypes for gene: DPM2 were changed from Congenital disorder of glycosylation, type Iu 615042 to Congenital disorder of glycosylation, type Iu 615042; seizures
Early onset or syndromic epilepsy v1.121 DPM2 Rebecca Foulger Publications for gene: DPM2 were set to 23109149
Early onset or syndromic epilepsy v1.120 DPM2 Rebecca Foulger Classified gene: DPM2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.120 DPM2 Rebecca Foulger Added comment: Comment on list classification: Reassessing rating of DPM2 during curation of GMS panel: Evidence remains insufficient for a diagnostic-rating (3 patients from 2 families in the literature: PMIDs 23109149 and 26453362).
Early onset or syndromic epilepsy v1.120 DPM2 Rebecca Foulger Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.119 DPM2 Rebecca Foulger commented on gene: DPM2: PMID:26453362: Fiumara et al. 2016 report a patient (patient 2) with Early-onset epileptic encephalopathy (seizure onset in first week). This girl has been previously reported in PMID:23109149 (patient 1 in Barone et al., 2012).
Early onset or syndromic epilepsy v1.119 DPM2 Rebecca Foulger commented on gene: DPM2
Adult onset leukodystrophy v0.7 ZFYVE26 Louise Daugherty Source Expert Review Green was added to ZFYVE26.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 TYROBP Louise Daugherty Source Expert Review Green was added to TYROBP.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 TUBB4A Louise Daugherty Source Expert Review Green was added to TUBB4A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 TREX1 Louise Daugherty Source Expert Review Green was added to TREX1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 TREM2 Louise Daugherty Source Expert Review Green was added to TREM2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 SPG11 Louise Daugherty Source Expert Review Green was added to SPG11.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 SAMHD1 Louise Daugherty Source Expert Review Green was added to SAMHD1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 RPS6KA3 Louise Daugherty Source Expert Review Green was added to RPS6KA3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 RNF216 Louise Daugherty Source Expert Review Green was added to RNF216.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 RNASET2 Louise Daugherty Source Expert Review Green was added to RNASET2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 RNASEH2C Louise Daugherty Source Expert Review Green was added to RNASEH2C.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 RNASEH2B Louise Daugherty Source Expert Review Green was added to RNASEH2B.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 RNASEH2A Louise Daugherty Source Expert Review Green was added to RNASEH2A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PTEN Louise Daugherty Source Expert Review Green was added to PTEN.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PSAP Louise Daugherty Source Expert Review Green was added to PSAP.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 POLR3B Louise Daugherty Source Expert Review Green was added to POLR3B.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 POLR3A Louise Daugherty Source Expert Review Green was added to POLR3A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 POLR1C Louise Daugherty Source Expert Review Green was added to POLR1C.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PLP1 Louise Daugherty Source Expert Review Green was added to PLP1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX7 Louise Daugherty Source Expert Review Green was added to PEX7.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX6 Louise Daugherty Source Expert Review Green was added to PEX6.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX5 Louise Daugherty Source Expert Review Green was added to PEX5.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX3 Louise Daugherty Source Expert Review Green was added to PEX3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX26 Louise Daugherty Source Expert Review Green was added to PEX26.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX2 Louise Daugherty Source Expert Review Green was added to PEX2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX19 Louise Daugherty Source Expert Review Green was added to PEX19.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX16 Louise Daugherty Source Expert Review Green was added to PEX16.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX14 Louise Daugherty Source Expert Review Green was added to PEX14.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX13 Louise Daugherty Source Expert Review Green was added to PEX13.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX12 Louise Daugherty Source Expert Review Green was added to PEX12.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX11B Louise Daugherty Source Expert Review Green was added to PEX11B.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX10 Louise Daugherty Source Expert Review Green was added to PEX10.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PEX1 Louise Daugherty Source Expert Review Green was added to PEX1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 PAH Louise Daugherty Source Expert Review Green was added to PAH.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 OCRL Louise Daugherty Source Expert Review Green was added to OCRL.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 NOTCH3 Louise Daugherty Source Expert Review Green was added to NOTCH3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 MTHFR Louise Daugherty Source Expert Review Green was added to MTHFR.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 MCOLN1 Louise Daugherty Source Expert Review Green was added to MCOLN1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 MARS Louise Daugherty Source Expert Review Green was added to MARS.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 LMNB1 Louise Daugherty Source Expert Review Green was added to LMNB1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 L2HGDH Louise Daugherty Source Expert Review Green was added to L2HGDH.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 KIF5A Louise Daugherty Source Expert Review Green was added to KIF5A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 HTRA1 Louise Daugherty Source Expert Review Green was added to HTRA1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 HMGCL Louise Daugherty Source Expert Review Green was added to HMGCL.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 HEXA Louise Daugherty Source Expert Review Green was added to HEXA.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 HEPACAM Louise Daugherty Source Expert Review Green was added to HEPACAM.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GLB1 Louise Daugherty Source Expert Review Green was added to GLB1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GLA Louise Daugherty Source Expert Review Green was added to GLA.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GJC2 Louise Daugherty Source Expert Review Green was added to GJC2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GJB1 Louise Daugherty Source Expert Review Green was added to GJB1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GJA1 Louise Daugherty Source Expert Review Green was added to GJA1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GFAP Louise Daugherty Source Expert Review Green was added to GFAP.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GBE1 Louise Daugherty Source Expert Review Green was added to GBE1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 GALC Louise Daugherty Source Expert Review Green was added to GALC.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 EIF2B5 Louise Daugherty Source Expert Review Green was added to EIF2B5.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 EIF2B4 Louise Daugherty Source Expert Review Green was added to EIF2B4.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 EIF2B3 Louise Daugherty Source Expert Review Green was added to EIF2B3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 EIF2B2 Louise Daugherty Source Expert Review Green was added to EIF2B2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 EIF2B1 Louise Daugherty Source Expert Review Green was added to EIF2B1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 EARS2 Louise Daugherty Source Expert Review Green was added to EARS2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 DARS2 Louise Daugherty Source Expert Review Green was added to DARS2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 DARS Louise Daugherty Source Expert Review Green was added to DARS.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 CYP27A1 Louise Daugherty Source Expert Review Green was added to CYP27A1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 CTSA Louise Daugherty Source Expert Review Green was added to CTSA.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 CTC1 Louise Daugherty Source Expert Review Green was added to CTC1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 CSF1R Louise Daugherty Source Expert Review Green was added to CSF1R.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 COL4A2 Louise Daugherty Source Expert Review Green was added to COL4A2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 COL4A1 Louise Daugherty Source Expert Review Green was added to COL4A1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 CLCN2 Louise Daugherty Source Expert Review Green was added to CLCN2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 ARSA Louise Daugherty Source Expert Review Green was added to ARSA.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 ALDH3A2 Louise Daugherty Source Expert Review Green was added to ALDH3A2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 ADAR Louise Daugherty Source Expert Review Green was added to ADAR.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 ABCD1 Louise Daugherty Source Expert Review Green was added to ABCD1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 AARS2 Louise Daugherty Source Expert Review Green was added to AARS2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.7 AARS Louise Daugherty Source Expert Review Green was added to AARS.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset leukodystrophy v0.6 ZFYVE26 Louise Daugherty Source NHS GMS was added to ZFYVE26.
Adult onset leukodystrophy v0.6 TYROBP Louise Daugherty Source NHS GMS was added to TYROBP.
Adult onset leukodystrophy v0.6 TUBB4A Louise Daugherty Source NHS GMS was added to TUBB4A.
Adult onset leukodystrophy v0.6 TREX1 Louise Daugherty Source NHS GMS was added to TREX1.
Adult onset leukodystrophy v0.6 TREM2 Louise Daugherty Source NHS GMS was added to TREM2.
Adult onset leukodystrophy v0.6 SPG11 Louise Daugherty Source NHS GMS was added to SPG11.
Adult onset leukodystrophy v0.6 SAMHD1 Louise Daugherty Source NHS GMS was added to SAMHD1.
Adult onset leukodystrophy v0.6 RPS6KA3 Louise Daugherty Source NHS GMS was added to RPS6KA3.
Adult onset leukodystrophy v0.6 RNF216 Louise Daugherty Source NHS GMS was added to RNF216.
Adult onset leukodystrophy v0.6 RNASET2 Louise Daugherty Source NHS GMS was added to RNASET2.
Adult onset leukodystrophy v0.6 RNASEH2C Louise Daugherty Source NHS GMS was added to RNASEH2C.
Adult onset leukodystrophy v0.6 RNASEH2B Louise Daugherty Source NHS GMS was added to RNASEH2B.
Adult onset leukodystrophy v0.6 RNASEH2A Louise Daugherty Source NHS GMS was added to RNASEH2A.
Adult onset leukodystrophy v0.6 PTEN Louise Daugherty Source NHS GMS was added to PTEN.
Adult onset leukodystrophy v0.6 PSAP Louise Daugherty Source NHS GMS was added to PSAP.
Adult onset leukodystrophy v0.6 POLR3B Louise Daugherty Source NHS GMS was added to POLR3B.
Adult onset leukodystrophy v0.6 POLR3A Louise Daugherty Source NHS GMS was added to POLR3A.
Adult onset leukodystrophy v0.6 POLR1C Louise Daugherty Source NHS GMS was added to POLR1C.
Adult onset leukodystrophy v0.6 PLP1 Louise Daugherty Source NHS GMS was added to PLP1.
Adult onset leukodystrophy v0.6 PEX7 Louise Daugherty Source NHS GMS was added to PEX7.
Adult onset leukodystrophy v0.6 PEX6 Louise Daugherty Source NHS GMS was added to PEX6.
Adult onset leukodystrophy v0.6 PEX5 Louise Daugherty Source NHS GMS was added to PEX5.
Adult onset leukodystrophy v0.6 PEX3 Louise Daugherty Source NHS GMS was added to PEX3.
Adult onset leukodystrophy v0.6 PEX26 Louise Daugherty Source NHS GMS was added to PEX26.
Adult onset leukodystrophy v0.6 PEX2 Louise Daugherty Source NHS GMS was added to PEX2.
Adult onset leukodystrophy v0.6 PEX19 Louise Daugherty Source NHS GMS was added to PEX19.
Adult onset leukodystrophy v0.6 PEX16 Louise Daugherty Source NHS GMS was added to PEX16.
Adult onset leukodystrophy v0.6 PEX14 Louise Daugherty Source NHS GMS was added to PEX14.
Adult onset leukodystrophy v0.6 PEX13 Louise Daugherty Source NHS GMS was added to PEX13.
Adult onset leukodystrophy v0.6 PEX12 Louise Daugherty Source NHS GMS was added to PEX12.
Adult onset leukodystrophy v0.6 PEX11B Louise Daugherty Source NHS GMS was added to PEX11B.
Adult onset leukodystrophy v0.6 PEX10 Louise Daugherty Source NHS GMS was added to PEX10.
Adult onset leukodystrophy v0.6 PEX1 Louise Daugherty Source NHS GMS was added to PEX1.
Adult onset leukodystrophy v0.6 PAH Louise Daugherty Source NHS GMS was added to PAH.
Adult onset leukodystrophy v0.6 OCRL Louise Daugherty Source NHS GMS was added to OCRL.
Adult onset leukodystrophy v0.6 NOTCH3 Louise Daugherty Source NHS GMS was added to NOTCH3.
Adult onset leukodystrophy v0.6 MTHFR Louise Daugherty Source NHS GMS was added to MTHFR.
Adult onset leukodystrophy v0.6 MCOLN1 Louise Daugherty Source NHS GMS was added to MCOLN1.
Adult onset leukodystrophy v0.6 MARS Louise Daugherty Source NHS GMS was added to MARS.
Adult onset leukodystrophy v0.6 LMNB1 Louise Daugherty Source NHS GMS was added to LMNB1.
Adult onset leukodystrophy v0.6 L2HGDH Louise Daugherty Source NHS GMS was added to L2HGDH.
Adult onset leukodystrophy v0.6 KIF5A Louise Daugherty Source NHS GMS was added to KIF5A.
Adult onset leukodystrophy v0.6 HTRA1 Louise Daugherty Source NHS GMS was added to HTRA1.
Adult onset leukodystrophy v0.6 HMGCL Louise Daugherty Source NHS GMS was added to HMGCL.
Adult onset leukodystrophy v0.6 HEXA Louise Daugherty Source NHS GMS was added to HEXA.
Adult onset leukodystrophy v0.6 HEPACAM Louise Daugherty Source NHS GMS was added to HEPACAM.
Adult onset leukodystrophy v0.6 GLB1 Louise Daugherty Source NHS GMS was added to GLB1.
Adult onset leukodystrophy v0.6 GLA Louise Daugherty Source NHS GMS was added to GLA.
Adult onset leukodystrophy v0.6 GJC2 Louise Daugherty Source NHS GMS was added to GJC2.
Adult onset leukodystrophy v0.6 GJB1 Louise Daugherty Source NHS GMS was added to GJB1.
Adult onset leukodystrophy v0.6 GJA1 Louise Daugherty Source NHS GMS was added to GJA1.
Adult onset leukodystrophy v0.6 GFAP Louise Daugherty Source NHS GMS was added to GFAP.
Adult onset leukodystrophy v0.6 GBE1 Louise Daugherty Source NHS GMS was added to GBE1.
Adult onset leukodystrophy v0.6 GALC Louise Daugherty Source NHS GMS was added to GALC.
Adult onset leukodystrophy v0.6 EIF2B5 Louise Daugherty Source NHS GMS was added to EIF2B5.
Adult onset leukodystrophy v0.6 EIF2B4 Louise Daugherty Source NHS GMS was added to EIF2B4.
Adult onset leukodystrophy v0.6 EIF2B3 Louise Daugherty Source NHS GMS was added to EIF2B3.
Adult onset leukodystrophy v0.6 EIF2B2 Louise Daugherty Source NHS GMS was added to EIF2B2.
Adult onset leukodystrophy v0.6 EIF2B1 Louise Daugherty Source NHS GMS was added to EIF2B1.
Adult onset leukodystrophy v0.6 EARS2 Louise Daugherty Source NHS GMS was added to EARS2.
Adult onset leukodystrophy v0.6 DARS2 Louise Daugherty Source NHS GMS was added to DARS2.
Adult onset leukodystrophy v0.6 DARS Louise Daugherty Source NHS GMS was added to DARS.
Adult onset leukodystrophy v0.6 CYP27A1 Louise Daugherty Source NHS GMS was added to CYP27A1.
Adult onset leukodystrophy v0.6 CTSA Louise Daugherty Source NHS GMS was added to CTSA.
Adult onset leukodystrophy v0.6 CTC1 Louise Daugherty Source NHS GMS was added to CTC1.
Adult onset leukodystrophy v0.6 CSF1R Louise Daugherty Source NHS GMS was added to CSF1R.
Adult onset leukodystrophy v0.6 COL4A2 Louise Daugherty Source NHS GMS was added to COL4A2.
Adult onset leukodystrophy v0.6 COL4A1 Louise Daugherty Source NHS GMS was added to COL4A1.
Adult onset leukodystrophy v0.6 CLCN2 Louise Daugherty Source NHS GMS was added to CLCN2.
Adult onset leukodystrophy v0.6 ARSA Louise Daugherty Source NHS GMS was added to ARSA.
Adult onset leukodystrophy v0.6 ALDH3A2 Louise Daugherty Source NHS GMS was added to ALDH3A2.
Adult onset leukodystrophy v0.6 ADAR Louise Daugherty Source NHS GMS was added to ADAR.
Adult onset leukodystrophy v0.6 ABCD1 Louise Daugherty Source NHS GMS was added to ABCD1.
Adult onset leukodystrophy v0.6 AARS2 Louise Daugherty Source NHS GMS was added to AARS2.
Adult onset leukodystrophy v0.6 AARS Louise Daugherty Source NHS GMS was added to AARS.
Early onset or syndromic epilepsy v1.119 BCKDHA Rebecca Foulger Publications for gene: BCKDHA were set to 2703538; 8037208; 9582350; 31119508
Early onset or syndromic epilepsy v1.118 BCKDHB Rebecca Foulger Publications for gene: BCKDHB were set to 31119508
Early onset or syndromic epilepsy v1.117 BCKDHB Rebecca Foulger Publications for gene: BCKDHB were set to
Early onset or syndromic epilepsy v1.116 BCKDHA Rebecca Foulger Publications for gene: BCKDHA were set to 2703538; 8037208; 9582350
Early onset or syndromic epilepsy v1.115 DBT Rebecca Foulger Tag watchlist was removed from gene: DBT.
Early onset or syndromic epilepsy v1.115 DBT Rebecca Foulger Phenotypes for gene: DBT were changed from Maple syrup urine disease, type II, 248600 to Maple syrup urine disease, type II, 248600; seizures; convulsions
Early onset or syndromic epilepsy v1.114 DBT Rebecca Foulger Publications for gene: DBT were set to
Early onset or syndromic epilepsy v1.113 DBT Rebecca Foulger Classified gene: DBT as Green List (high evidence)
Early onset or syndromic epilepsy v1.113 DBT Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following publication of two 2019 papers (PMID:31112740 and PMID:31119508) who report MSUD patients with seizures and biallelic variants in DBT. Each paper reports individuals from a different ethnic group. Sufficient unrelated cases for a diagnostic-green rating.
Early onset or syndromic epilepsy v1.113 DBT Rebecca Foulger Gene: dbt has been classified as Green List (High Evidence).
Adult onset leukodystrophy v0.5 ZFYVE26 Louise Daugherty gene: ZFYVE26 was added
gene: ZFYVE26 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: ZFYVE26 was set to
Adult onset leukodystrophy v0.5 TYROBP Louise Daugherty gene: TYROBP was added
gene: TYROBP was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: TYROBP was set to
Adult onset leukodystrophy v0.5 TUBB4A Louise Daugherty gene: TUBB4A was added
gene: TUBB4A was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: TUBB4A was set to
Adult onset leukodystrophy v0.5 TREX1 Louise Daugherty gene: TREX1 was added
gene: TREX1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: TREX1 was set to
Adult onset leukodystrophy v0.5 TREM2 Louise Daugherty gene: TREM2 was added
gene: TREM2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: TREM2 was set to
Adult onset leukodystrophy v0.5 SPG11 Louise Daugherty gene: SPG11 was added
gene: SPG11 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: SPG11 was set to
Adult onset leukodystrophy v0.5 SAMHD1 Louise Daugherty gene: SAMHD1 was added
gene: SAMHD1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: SAMHD1 was set to
Adult onset leukodystrophy v0.5 RPS6KA3 Louise Daugherty gene: RPS6KA3 was added
gene: RPS6KA3 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: RPS6KA3 was set to
Adult onset leukodystrophy v0.5 RNF216 Louise Daugherty gene: RNF216 was added
gene: RNF216 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: RNF216 was set to
Adult onset leukodystrophy v0.5 RNASET2 Louise Daugherty gene: RNASET2 was added
gene: RNASET2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: RNASET2 was set to
Adult onset leukodystrophy v0.5 RNASEH2C Louise Daugherty gene: RNASEH2C was added
gene: RNASEH2C was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: RNASEH2C was set to
Adult onset leukodystrophy v0.5 RNASEH2B Louise Daugherty gene: RNASEH2B was added
gene: RNASEH2B was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: RNASEH2B was set to
Adult onset leukodystrophy v0.5 RNASEH2A Louise Daugherty gene: RNASEH2A was added
gene: RNASEH2A was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: RNASEH2A was set to
Adult onset leukodystrophy v0.5 PTEN Louise Daugherty gene: PTEN was added
gene: PTEN was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PTEN was set to
Adult onset leukodystrophy v0.5 PSAP Louise Daugherty gene: PSAP was added
gene: PSAP was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PSAP was set to
Adult onset leukodystrophy v0.5 POLR3B Louise Daugherty gene: POLR3B was added
gene: POLR3B was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: POLR3B was set to
Adult onset leukodystrophy v0.5 POLR3A Louise Daugherty gene: POLR3A was added
gene: POLR3A was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: POLR3A was set to
Adult onset leukodystrophy v0.5 POLR1C Louise Daugherty gene: POLR1C was added
gene: POLR1C was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: POLR1C was set to
Adult onset leukodystrophy v0.5 PLP1 Louise Daugherty gene: PLP1 was added
gene: PLP1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PLP1 was set to
Adult onset leukodystrophy v0.5 PEX7 Louise Daugherty gene: PEX7 was added
gene: PEX7 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX7 was set to
Adult onset leukodystrophy v0.5 PEX6 Louise Daugherty gene: PEX6 was added
gene: PEX6 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX6 was set to
Adult onset leukodystrophy v0.5 PEX5 Louise Daugherty gene: PEX5 was added
gene: PEX5 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX5 was set to
Adult onset leukodystrophy v0.5 PEX3 Louise Daugherty gene: PEX3 was added
gene: PEX3 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX3 was set to
Adult onset leukodystrophy v0.5 PEX26 Louise Daugherty gene: PEX26 was added
gene: PEX26 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX26 was set to
Adult onset leukodystrophy v0.5 PEX2 Louise Daugherty gene: PEX2 was added
gene: PEX2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX2 was set to
Adult onset leukodystrophy v0.5 PEX19 Louise Daugherty gene: PEX19 was added
gene: PEX19 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX19 was set to
Adult onset leukodystrophy v0.5 PEX16 Louise Daugherty gene: PEX16 was added
gene: PEX16 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX16 was set to
Adult onset leukodystrophy v0.5 PEX14 Louise Daugherty gene: PEX14 was added
gene: PEX14 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX14 was set to
Adult onset leukodystrophy v0.5 PEX13 Louise Daugherty gene: PEX13 was added
gene: PEX13 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX13 was set to
Adult onset leukodystrophy v0.5 PEX12 Louise Daugherty gene: PEX12 was added
gene: PEX12 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX12 was set to
Adult onset leukodystrophy v0.5 PEX11B Louise Daugherty gene: PEX11B was added
gene: PEX11B was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX11B was set to
Adult onset leukodystrophy v0.5 PEX10 Louise Daugherty gene: PEX10 was added
gene: PEX10 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX10 was set to
Adult onset leukodystrophy v0.5 PEX1 Louise Daugherty gene: PEX1 was added
gene: PEX1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PEX1 was set to
Adult onset leukodystrophy v0.5 PAH Louise Daugherty gene: PAH was added
gene: PAH was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: PAH was set to
Adult onset leukodystrophy v0.5 OCRL Louise Daugherty gene: OCRL was added
gene: OCRL was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: OCRL was set to
Adult onset leukodystrophy v0.5 NOTCH3 Louise Daugherty gene: NOTCH3 was added
gene: NOTCH3 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: NOTCH3 was set to
Adult onset leukodystrophy v0.5 MTHFR Louise Daugherty gene: MTHFR was added
gene: MTHFR was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: MTHFR was set to
Adult onset leukodystrophy v0.5 MCOLN1 Louise Daugherty gene: MCOLN1 was added
gene: MCOLN1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: MCOLN1 was set to
Adult onset leukodystrophy v0.5 MARS Louise Daugherty gene: MARS was added
gene: MARS was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: MARS was set to
Adult onset leukodystrophy v0.5 LMNB1 Louise Daugherty gene: LMNB1 was added
gene: LMNB1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: LMNB1 was set to
Adult onset leukodystrophy v0.5 L2HGDH Louise Daugherty gene: L2HGDH was added
gene: L2HGDH was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: L2HGDH was set to
Adult onset leukodystrophy v0.5 KIF5A Louise Daugherty gene: KIF5A was added
gene: KIF5A was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: KIF5A was set to
Adult onset leukodystrophy v0.5 HTRA1 Louise Daugherty gene: HTRA1 was added
gene: HTRA1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: HTRA1 was set to
Adult onset leukodystrophy v0.5 HMGCL Louise Daugherty gene: HMGCL was added
gene: HMGCL was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: HMGCL was set to
Adult onset leukodystrophy v0.5 HEXA Louise Daugherty gene: HEXA was added
gene: HEXA was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: HEXA was set to
Adult onset leukodystrophy v0.5 HEPACAM Louise Daugherty gene: HEPACAM was added
gene: HEPACAM was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: HEPACAM was set to
Adult onset leukodystrophy v0.5 GLB1 Louise Daugherty gene: GLB1 was added
gene: GLB1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GLB1 was set to
Adult onset leukodystrophy v0.5 GLA Louise Daugherty gene: GLA was added
gene: GLA was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GLA was set to
Adult onset leukodystrophy v0.5 GJC2 Louise Daugherty gene: GJC2 was added
gene: GJC2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GJC2 was set to
Adult onset leukodystrophy v0.5 GJB1 Louise Daugherty gene: GJB1 was added
gene: GJB1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GJB1 was set to
Adult onset leukodystrophy v0.5 GJA1 Louise Daugherty gene: GJA1 was added
gene: GJA1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GJA1 was set to
Adult onset leukodystrophy v0.5 GFAP Louise Daugherty gene: GFAP was added
gene: GFAP was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GFAP was set to
Adult onset leukodystrophy v0.5 GBE1 Louise Daugherty gene: GBE1 was added
gene: GBE1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GBE1 was set to
Adult onset leukodystrophy v0.5 GALC Louise Daugherty gene: GALC was added
gene: GALC was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: GALC was set to
Adult onset leukodystrophy v0.5 EIF2B5 Louise Daugherty gene: EIF2B5 was added
gene: EIF2B5 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: EIF2B5 was set to
Adult onset leukodystrophy v0.5 EIF2B4 Louise Daugherty gene: EIF2B4 was added
gene: EIF2B4 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: EIF2B4 was set to
Adult onset leukodystrophy v0.5 EIF2B3 Louise Daugherty gene: EIF2B3 was added
gene: EIF2B3 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: EIF2B3 was set to
Adult onset leukodystrophy v0.5 EIF2B2 Louise Daugherty gene: EIF2B2 was added
gene: EIF2B2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: EIF2B2 was set to
Adult onset leukodystrophy v0.5 EIF2B1 Louise Daugherty gene: EIF2B1 was added
gene: EIF2B1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: EIF2B1 was set to
Adult onset leukodystrophy v0.5 EARS2 Louise Daugherty gene: EARS2 was added
gene: EARS2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: EARS2 was set to
Adult onset leukodystrophy v0.5 DARS2 Louise Daugherty gene: DARS2 was added
gene: DARS2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: DARS2 was set to
Adult onset leukodystrophy v0.5 DARS Louise Daugherty gene: DARS was added
gene: DARS was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: DARS was set to
Adult onset leukodystrophy v0.5 CYP27A1 Louise Daugherty gene: CYP27A1 was added
gene: CYP27A1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: CYP27A1 was set to
Adult onset leukodystrophy v0.5 CTSA Louise Daugherty gene: CTSA was added
gene: CTSA was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: CTSA was set to
Adult onset leukodystrophy v0.5 CTC1 Louise Daugherty gene: CTC1 was added
gene: CTC1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: CTC1 was set to
Adult onset leukodystrophy v0.5 CSF1R Louise Daugherty gene: CSF1R was added
gene: CSF1R was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: CSF1R was set to
Adult onset leukodystrophy v0.5 COL4A2 Louise Daugherty gene: COL4A2 was added
gene: COL4A2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: COL4A2 was set to
Adult onset leukodystrophy v0.5 COL4A1 Louise Daugherty gene: COL4A1 was added
gene: COL4A1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: COL4A1 was set to
Adult onset leukodystrophy v0.5 CLCN2 Louise Daugherty gene: CLCN2 was added
gene: CLCN2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: CLCN2 was set to
Adult onset leukodystrophy v0.5 ARSA Louise Daugherty gene: ARSA was added
gene: ARSA was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: ARSA was set to
Adult onset leukodystrophy v0.5 ALDH3A2 Louise Daugherty gene: ALDH3A2 was added
gene: ALDH3A2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: ALDH3A2 was set to
Adult onset leukodystrophy v0.5 ADAR Louise Daugherty gene: ADAR was added
gene: ADAR was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: ADAR was set to
Adult onset leukodystrophy v0.5 ABCD1 Louise Daugherty gene: ABCD1 was added
gene: ABCD1 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: ABCD1 was set to
Adult onset leukodystrophy v0.5 AARS2 Louise Daugherty gene: AARS2 was added
gene: AARS2 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: AARS2 was set to
Adult onset leukodystrophy v0.5 AARS Louise Daugherty gene: AARS was added
gene: AARS was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH
Mode of inheritance for gene: AARS was set to
Likely inborn error of metabolism v1.60 PARS2 Eleanor Williams Added comment: Comment on phenotypes: Phenotype association added to OMIM in May 2019
Likely inborn error of metabolism v1.60 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome. to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome.
Early onset or syndromic epilepsy v1.112 DBT Rebecca Foulger commented on gene: DBT: PMID:31112740. Yang et al 2019 identify a Chinese patient with MSUD (Patient 2) with compound het DBT variants: missense p.Leu69Arg and nonsense R291*. Patient 2 was recorded with Convulsions (Table 1). Leu69 is located in the LBD of the encoded BCKD protein, and therefore likely to affect the function of the protein. Segregation analysis was not performed. The 1000 Genome Project data was used to filter the data, and variants were validated by Sanger sequencing.
Likely inborn error of metabolism v1.60 PARS2 Eleanor Williams Added comment: Comment on phenotypes: Phenotype association added to OMIM in May 2019
Likely inborn error of metabolism v1.60 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome. to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome.
Intellectual disability v2.938 DBT Rebecca Foulger commented on gene: DBT
Intellectual disability v2.938 DBT Rebecca Foulger Publications for gene: DBT were set to
Early onset or syndromic epilepsy v1.112 PARS2 Eleanor Williams Classified gene: PARS2 as Green List (high evidence)
Early onset or syndromic epilepsy v1.112 PARS2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as found in more than 3 cases and variants segregate with the condition in all families.
Early onset or syndromic epilepsy v1.112 PARS2 Eleanor Williams Gene: pars2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.111 PARS2 Eleanor Williams gene: PARS2 was added
gene: PARS2 was added to Genetic epilepsy syndromes. Sources: Other
Mode of inheritance for gene: PARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PARS2 were set to 22237560; 25629079; 27290639; 29410512; 29410512; 29915213
Phenotypes for gene: PARS2 were set to Epileptic encephalopathy, early infantile, 75, 618437
Review for gene: PARS2 was set to GREEN
Added comment: An association of this gene with Epileptic encephalopathy, early infantile, 75 (#618437) has recently been added to OMIM (May 2019). The gene is predicted to encode for prolyl-tRNA synthetase.

Compound heterozygous mutations in PARS2 have been reported in individuals from 4 unrelated families (Swedish (PMID: 22237560, 25629079), Polish (PMID: 27290639, 29410512), Japanese (PMID: 28077841), Chinese (PMID: 29915213). In all cases the children presented with seizures/epilepsy under the age of 1 year. Other clinical features included developmental delay in all and dilated cardiomyopathy in 2 patients.

Of the seven variants reported six are missense and one is a 1 bp duplication resulting in a frameshift. In the publication about the Chinese family (PMID: 29915213) OMIM report that the missense variants were assessed as being pathogenic according to ACMG guidelines.

In all families the variants segregated with the disorder.

Functional studies were only carried out in one case (PMID: 25629079). In this case the levels of prolyl-tRNA synthetase in the patient did not differ significantly from control levels when normalized to GAPDH.
Sources: Other
Early onset or syndromic epilepsy v1.110 DBT Rebecca Foulger commented on gene: DBT: PMID:31119508. Abiri et al. 2019 investigated the mutation spectrum of MSUD patients in 40 unrelated Iranian families. 5 patients (P36-P40) had homozygous or compound het variants in DBT. 4/5 of these patients had seizures reported. Four of the DBT variants were novel. None of the variants are present in controls including ExAC and the Iranome. Different variants reported in each of the 5 patients suggesting the patients are unrelated.
Familial chylomicronaemia syndrome (FCS) v0.2 LPL Sarah Leigh gene: LPL was added
gene: LPL was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: LPL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LPL were set to Lipoprotein lipase deficiency 238600; Combined hyperlipidemia, familial 144250
Familial chylomicronaemia syndrome (FCS) v0.2 LMF1 Sarah Leigh gene: LMF1 was added
gene: LMF1 was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: LMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LMF1 were set to Lipase deficiency, combined 246650
Familial chylomicronaemia syndrome (FCS) v0.2 LIPI Sarah Leigh gene: LIPI was added
gene: LIPI was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: LIPI was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LIPI were set to hypertriglyceridemia
Familial chylomicronaemia syndrome (FCS) v0.2 GPIHBP1 Sarah Leigh gene: GPIHBP1 was added
gene: GPIHBP1 was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type 1D 615947
Familial chylomicronaemia syndrome (FCS) v0.2 GPD1 Sarah Leigh gene: GPD1 was added
gene: GPD1 was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: GPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPD1 were set to Hypertriglyceridemia, transient infantile 614480
Familial chylomicronaemia syndrome (FCS) v0.2 CREB3L3 Sarah Leigh gene: CREB3L3 was added
gene: CREB3L3 was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CREB3L3 were set to 29954705; 21666694; 26427795
Phenotypes for gene: CREB3L3 were set to monogenic dominant hypertriglyceridemia associated with CREB3L3
Familial chylomicronaemia syndrome (FCS) v0.2 APOE Sarah Leigh gene: APOE was added
gene: APOE was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: APOE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: APOE were set to Sea-blue histiocyte disease 269600; Hyperlipoproteinemia, type III 617347; Lipoprotein glomerulopathy 611771; Alzheimer disease-2 104310
Familial chylomicronaemia syndrome (FCS) v0.2 APOC2 Sarah Leigh gene: APOC2 was added
gene: APOC2 was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: APOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: APOC2 were set to Hyperlipoproteinemia, type Ib 207750
Familial chylomicronaemia syndrome (FCS) v0.2 APOB Sarah Leigh gene: APOB was added
gene: APOB was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: APOB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: APOB were set to Hypercholesterolemia, familial, 2 144010; Hypobetalipoproteinemia 615558
Familial chylomicronaemia syndrome (FCS) v0.2 APOA5 Sarah Leigh gene: APOA5 was added
gene: APOA5 was added to Lipoprotein lipase deficiency. Sources: NHS GMS,South West GLH,Expert Review Green
Mode of inheritance for gene: APOA5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: APOA5 were set to Hyperchylomicronemia, late-onset 144650
Mitochondrial disorders v1.402 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome; Epileptic encephalopathy, early infantile, 75, 618437 to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Alpers syndrome; Epileptic encephalopathy, early infantile, 75, 618437
Early onset or syndromic epilepsy v1.110 GNB5 Rebecca Foulger Phenotypes for gene: GNB5 were changed from Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182 to Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182; early infantile epileptic encephalopathy (EIEE)
Early onset or syndromic epilepsy v1.109 TRAPPC6B Rebecca Foulger changed review comment from: In 2 patients from a consanguineous family, PMID:28397838 (Harripaul et al. 2018) identified a homozygous truncating variant in TRAPPC6N. The patients were selected for non-syndromic ID, which often presents with epilepsy but seizures were not discussed in the patients.; to: In 2 patients from a consanguineous family, PMID:28397838 (Harripaul et al. 2018) identified a homozygous truncating variant in TRAPPC6N. The patients were selected for non-syndromic ID, which often presents with epilepsy .
Early onset or syndromic epilepsy v1.109 TRAPPC12 Rebecca Foulger changed review comment from: Comment on list classification: Kept rating as Amber: 2 literature cases only in PMID:28777934. Seizures are a phenotype of both cases but further cases required for a diagnostic rating.; to: Comment on list classification: Kept rating as Amber: 2 families only in PMID:28777934. Seizures are a phenotype in 2/3 of the patients (one patient from each family).
Early onset or syndromic epilepsy v1.109 TRAPPC12 Rebecca Foulger changed review comment from: In 3 patients from 2 unrelated families with early-onset progressive encephalopathy with brain atrophy and spasticity (MIM:617669), Milev et al. (2017, PMID:28777934) identified homozygous or compound heterozygous mutations in the TRAPPC12 gene. The article text reports epilepsy in 2/3 patients (the patient from family I, and one of the sisters from family II; the other sister showed monoclonic jerks only).; to: In 3 patients from 2 unrelated families with early-onset progressive encephalopathy with brain atrophy and spasticity (MIM:617669), Milev et al. (2017, PMID:28777934) identified homozygous or compound heterozygous mutations in the TRAPPC12 gene. Epilepsy is reported in 2/3 patients (the patient from family I, and one of the sisters from family II; the other sister showed monoclonic jerks only).
Early onset or syndromic epilepsy v1.109 TRAPPC12 Rebecca Foulger changed review comment from: In 3 patients from 2 unrelated families with early-onset progressive encephalopathy with brain atrophy and spasticity (MIM:617669), Milev et al. (2017, PMID:28777934) identified homozygous or compound heterozygous mutations in the TRAPPC12 gene. The article text reports seizures in all 3 patients.; to: In 3 patients from 2 unrelated families with early-onset progressive encephalopathy with brain atrophy and spasticity (MIM:617669), Milev et al. (2017, PMID:28777934) identified homozygous or compound heterozygous mutations in the TRAPPC12 gene. The article text reports epilepsy in 2/3 patients (the patient from family I, and one of the sisters from family II; the other sister showed monoclonic jerks only).
Adult onset hereditary spastic paraplegia v0.155 ARL6IP1 Louise Daugherty Phenotypes for gene: ARL6IP1 were changed from 24482476; 28471035 to Spastic paraplegia 61, autosomal recessive, 615685
Proteinuric renal disease v1.216 DLC1 Eleanor Williams Classified gene: DLC1 as Green List (high evidence)
Proteinuric renal disease v1.216 DLC1 Eleanor Williams Added comment: Comment on list classification: Plausible disease causing variants found in more than 3 cases.
Proteinuric renal disease v1.216 DLC1 Eleanor Williams Gene: dlc1 has been classified as Green List (High Evidence).
Intellectual disability v2.937 TRAPPC12 Louise Daugherty commented on gene: TRAPPC12: Did not upgrade gene on the Genetic Epilepsy Syndromes panel as there was no phenotype of epilepsy in the third case.
Early onset or syndromic epilepsy v1.109 TRAF7 Rebecca Foulger Tag watchlist tag was added to gene: TRAF7.
Early onset or syndromic epilepsy v1.109 TRAF7 Rebecca Foulger Classified gene: TRAF7 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.109 TRAF7 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber following external review by Konstantinos Varvagiannis: currently seizures are not a consistent phenotype (2/7 patients in PMID:29961569). Disease confidence rating in Gene2Phenotype is 'probable' for the disorder: Developmental Delay Congenital Anomalies and Dysmorphic Features. Added watchlist tag as further cases of seizures/epilepsy are required for a Green rating.
Early onset or syndromic epilepsy v1.109 TRAF7 Rebecca Foulger Gene: traf7 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.108 TRAF7 Rebecca Foulger commented on gene: TRAF7: PMID 29961569: Tokita et al, 2018 report TRAF7 missense variants in seven unrelated individuals. Seizures reported in two patients, plus 'possible absence seizures' reported in patient 6.
Early onset or syndromic epilepsy v1.108 SMC1A Rebecca Foulger Added comment: Comment on mode of inheritance: Set MOI to X-linked dominant to match Gene2Phenotype and the MOI for SMC1A on the Intellectual disability panel. So far, mostly females have gross gene alterations of SMC1A, which are likely not tolerated in males (PMID:19842212).
Early onset or syndromic epilepsy v1.108 SMC1A Rebecca Foulger Mode of inheritance for gene: SMC1A was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v1.107 SMC1A Rebecca Foulger Classified gene: SMC1A as Green List (high evidence)
Early onset or syndromic epilepsy v1.107 SMC1A Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on external review by Deb Pal, and a literature review. Plenty of recent papers reporting SMC1A variants causing epilepsy in female patients (e.g. PMIDs:31098032, 28677859, 28166369, 26752331,26386245,26358754). SMC1A variants can cause Cornelia de Lange syndrome (CdLS) but can also cause ID and epilepsy in the absence of CdLS features (PMID:31185419). Plus 'confirmed' rating in Gene2Phenotype for EPILEPTIC ENCEPHALOPATHY.
Early onset or syndromic epilepsy v1.107 SMC1A Rebecca Foulger Gene: smc1a has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.106 SMC1A Rebecca Foulger Publications for gene: SMC1A were set to 16604071; 17273969; 31185419; 31098032
Early onset or syndromic epilepsy v1.105 SMC1A Rebecca Foulger Publications for gene: SMC1A were set to 16604071; 17273969; 31185419
Early onset or syndromic epilepsy v1.104 SMC1A Rebecca Foulger Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY to Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY; Rett-like phenotype
Early onset or syndromic epilepsy v1.103 SMC1A Rebecca Foulger Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2 300590 to Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY
Early onset or syndromic epilepsy v1.102 SMC1A Rebecca Foulger Publications for gene: SMC1A were set to 16604071; 17273969
Early onset or syndromic epilepsy v1.101 SMC1A Rebecca Foulger changed review comment from: PMID:31185419: Oguni et al 2019 report a missense variant (c.2683C>G:pArg895Gly) of SMC1A affecting a daughter (proband) and her mother. The daughter began having epileptic seizures age 2 years 1 month, progressing into cluster seizures. The mother began to have cluter seizures age 12 and had moderate ID. Neither individual had typical CdLS morphological features. Sequencing confirmed the variant was present in daughter and mother, but not other maternal family members. Blood samples from the paternal side were unavailable.; to: PMID:31185419: Oguni et al 2019 report a missense variant (c.2683C>G:pArg895Gly) of SMC1A affecting a daughter (proband) and her mother. The daughter began having epileptic seizures age 2 years 1 month, progressing into cluster seizures. The mother began to have cluster seizures age 12 and had moderate ID. Neither individual had typical CdLS morphological features. Sequencing confirmed the variant was present in daughter and mother, but not other maternal family members. Blood samples from the paternal side were unavailable.
Early onset or syndromic epilepsy v1.101 SMC1A Rebecca Foulger commented on gene: SMC1A
Rare multisystem ciliopathy disorders v1.119 CFAP43 Rebecca Foulger Phenotypes for gene: CFAP43 were changed from Spermatogenic failure 19 617592 to Spermatogenic failure 19, 617592
Rare multisystem ciliopathy disorders v1.118 DNAH1 Rebecca Foulger Phenotypes for gene: DNAH1 were changed from Spermatogenic failure 18 617576 to Spermatogenic failure 18, 617576; ?Ciliary dyskinesia, primary, 37, 617577
Rare multisystem ciliopathy disorders v1.117 DNAH1 Rebecca Foulger Classified gene: DNAH1 as Red List (low evidence)
Rare multisystem ciliopathy disorders v1.117 DNAH1 Rebecca Foulger Added comment: Comment on list classification: Downgraded Spermatogenic failure gene DNAH1 from Green to Red on the Rare Multisystem ciliopathies panel on advice from the Genomics England clinical team: by definition, the phenotype is not a multisystem ciliopathy. DNAH1 also has a ciliary dyskinesia phenotype (MIM:617577) but there is limited evidence for this.
Rare multisystem ciliopathy disorders v1.117 DNAH1 Rebecca Foulger Gene: dnah1 has been classified as Red List (Low Evidence).
Rare multisystem ciliopathy disorders v1.116 CFAP43 Rebecca Foulger Classified gene: CFAP43 as Red List (low evidence)
Rare multisystem ciliopathy disorders v1.116 CFAP43 Rebecca Foulger Added comment: Comment on list classification: Downgraded the Spermatogenic failure gene CFAP43 from Green to Red on the Rare Multisystem ciliopathies panel on advice from the Genomics England clinical team: by definition, the phenotype is not a multisystem ciliopathy.
Rare multisystem ciliopathy disorders v1.116 CFAP43 Rebecca Foulger Gene: cfap43 has been classified as Red List (Low Evidence).
Intellectual disability v2.937 USP7 Rebecca Foulger Phenotypes for gene: USP7 were changed from to Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism
Intellectual disability v2.936 USP7 Rebecca Foulger Classified gene: USP7 as Amber List (moderate evidence)
Intellectual disability v2.936 USP7 Rebecca Foulger Gene: usp7 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.935 USP7 Rebecca Foulger Classified gene: USP7 as Red List (low evidence)
Intellectual disability v2.935 USP7 Rebecca Foulger Added comment: Comment on list classification: USP7 was rated Green by Konstantinos Varvagiannis. Not currently associated with a disorder in OMIM, but has a 'possible' Disease confidence in Gene2Phenotype for the disorder: Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism (based on PMID:26365382). There is now a 2019 paper in addition to PMID:26365382 (PMID:30679821). In total, 22/23 individuals have an ID/DD phenotype, and 23/23 have speech delay. However, the Tyr143Ter variant described by both PMID:26365382 and PMID:30679821 is a VUS, and the microdeletions in other patients cover additional genes (PMID:26365382, Figure 5). Plus three patients in PMID:30679821 harbour variants in additional genes. Therefore although the phenotype is relevant, I have updated the rating from Red to Amber until there is more evidence that USP7 variants are causative.
Intellectual disability v2.935 USP7 Rebecca Foulger Gene: usp7 has been classified as Red List (Low Evidence).
Intellectual disability v2.934 USP7 Rebecca Foulger Mode of inheritance for gene: USP7 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v2.933 USP7 Rebecca Foulger commented on gene: USP7: PMID:30679821: Fountain et al., 2019 report on the clinical and genetic spectrum of 16 new and 7 previously reported (by PMID:26365382) individuals with USP7 heterozygous de novo variants.
The variants include 2 deletions, 3 nonsense, 3 splice site variants and 8 missense variants. Speech delay was seen in 23/23 patients, and ID/DD was seen in 22/23 patients. Note that Patients 18 and 20 harbor additional variants in TMEM106B and SLC2A1, Patient 19 also has a de novo heterozygous 102.5-kb mosaic loss of uncertain significance at 10q21.1.
Intellectual disability v2.933 USP7 Rebecca Foulger commented on gene: USP7
Early onset or syndromic epilepsy v1.101 USP7 Rebecca Foulger Classified gene: USP7 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.101 USP7 Rebecca Foulger Added comment: Comment on list classification: USP7 was added to the panel and rated Green by Konstantinos Varvagiannis. Not currently associated with a disorder in OMIM, but has a 'possible' Disease confidence in Gene2Phenotype for the disorder: Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism (based on PMID:26365382). There is now a 2019 paper in addition to PMID:26365382 (PMID:30679821). In total, nearly half (10/22) individuals have a seizure phenotype. However, the Tyr143Ter variant described by both PMID:26365382 and PMID:30679821 is a VUS, and the microdeletions in other patients cover additional genes (PMID:26365382 Figure 5). Plus three patients in PMID:30679821 harbour variants in additional genes. Rated Amber until there is more evidence that USP7 variants are causative for the seizure phenotype.
Early onset or syndromic epilepsy v1.101 USP7 Rebecca Foulger Gene: usp7 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.100 USP7 Rebecca Foulger commented on gene: USP7: PMID:30679821: Fountain et al., 2019 report on the clinical and genetic spectrum of 16 new and 7 previously reported (by PMID:26365382) individuals with USP7 heterozygous de novo variants. The variants include 2 deletions, 3 nonsense, 3 splice site variants and 8 missense variants. Seizures are recorded in 10/22 patients. Note that Patients 18 and 20 harbor additional variants in TMEM106B and SLC2A1, Patient 19 also has a de novo heterozygous 102.5-kb mosaic loss of uncertain significance at 10q21.1.
Early onset or syndromic epilepsy v1.100 USP7 Rebecca Foulger commented on gene: USP7
Early onset or syndromic epilepsy v1.100 USP7 Rebecca Foulger Phenotypes for gene: USP7 were changed from Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism to Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism
Early onset or syndromic epilepsy v1.100 USP7 Rebecca Foulger Phenotypes for gene: USP7 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Behavioral abnormality; Seizures; Abnormality of brain morphology; Hypogonadism to Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism
Familial hypercholesterolaemia v1.24 APOE Sarah Leigh Added comment: Comment on phenotypes: Including hypercholesterolaemia
Familial hypercholesterolaemia v1.24 APOE Sarah Leigh Phenotypes for gene: APOE were changed from Autosomal dominant hypercholesterolaemia to Hyperlipoproteinemia, type III 617347
Familial hypercholesterolaemia v1.23 CYP27A1 Sarah Leigh Publications for gene: CYP27A1 were set to
Laterality disorders and isomerism v0.41 DNAH1 Louise Daugherty edited their review of gene: DNAH1: Changed rating: AMBER
Lipodystrophy - childhood onset v1.4 CAV1 Ivone Leong Publications for gene: CAV1 were set to PMID: 18390817; 18237401; 18211975; 25898808; 26176221; 27717241; 11739396; 23049990
Laterality disorders and isomerism v0.41 DNAH1 Louise Daugherty Classified gene: DNAH1 as Amber List (moderate evidence)
Laterality disorders and isomerism v0.41 DNAH1 Louise Daugherty Added comment: Comment on list classification: This gene was reviewed by the respiratory working group as part of the GMS. The evidence was considered sufficient only for an amber rating for PCD on the 'Respiratory ciliopathies including non-CF bronchiectasis' panel, as most homozygote knockouts have spermatogenic failure, no other PCD symptoms. PCD association is based on single pair of sisters with unvalidated missense, therefore as the phenotype is the same for both GMS panels, it was decided by the Genomics England clinical team to downgrade from Green to Amber, given it is the same phenotype associated with this gene, as the same GMS test group are overseeing both panels.
Laterality disorders and isomerism v0.41 DNAH1 Louise Daugherty Gene: dnah1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.99 PIGH Rebecca Foulger Classified gene: PIGH as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.99 PIGH Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber following review of Literature evidence. Although Zornitza rates as Green, PIGH is not yet associated with a disorder in Gene2Phenotype. There are only two relevant papers in the literature: PMID:29573052 report two siblings, and the individual in PMID:29603516 had only febrile seizures (no epilepsy).
Early onset or syndromic epilepsy v1.99 PIGH Rebecca Foulger Gene: pigh has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.98 PIGH Rebecca Foulger changed review comment from: PMID:29603516: Nguyen et al., 2018 identified an individual with a missense variant (p.Ser103Pro) in gene PIGH. The affected individual had hypotonia, moderate developmental delay, and autism. The proband did not have epilepsy; however, he did have two episodes of febrile seizures.; to: PMID:29603516: Nguyen et al., 2018 identified an individual with a missense variant (p.Ser103Pro) in gene PIGH. The affected individual who was born of consanguineous Indian parents had hypotonia, moderate developmental delay, and autism. The proband did not have epilepsy; however, he did have two episodes of febrile seizures.
Early onset or syndromic epilepsy v1.98 PIGH Rebecca Foulger Added comment: Comment on publications: PMID:29603510 isn't relevant to epilepsy so haven't included in the Publication field. Zornitza probably meant PMID:29603516.
Early onset or syndromic epilepsy v1.98 PIGH Rebecca Foulger Publications for gene: PIGH were set to 29603516; 29573052
Early onset or syndromic epilepsy v1.97 PIGH Rebecca Foulger commented on gene: PIGH: PMID:29603516: Nguyen et al., 2018 identified an individual with a missense variant (p.Ser103Pro) in gene PIGH. The affected individual had hypotonia, moderate developmental delay, and autism. The proband did not have epilepsy; however, he did have two episodes of febrile seizures.
Early onset or syndromic epilepsy v1.97 PIGH Rebecca Foulger commented on gene: PIGH
Early onset or syndromic epilepsy v1.97 PIGH Rebecca Foulger Phenotypes for gene: PIGH were changed from Glycosylphosphatidylinositol biosynthesis defect 17 618010 to Glycosylphosphatidylinositol biosynthesis defect 17, 618010; epilepsy; febrile seizures
Intellectual disability v2.933 TRAF7 Rebecca Foulger Classified gene: TRAF7 as Green List (high evidence)
Intellectual disability v2.933 TRAF7 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following advice from the Genomics England clinical team that the combination of motor and speech delay would be regarded by many clinicians as equivalent to global developmental delay.
Intellectual disability v2.933 TRAF7 Rebecca Foulger Gene: traf7 has been classified as Green List (High Evidence).
Intellectual disability v2.932 TRAF7 Rebecca Foulger Publications for gene: TRAF7 were set to 29961569; 27479843; 28135719
Intellectual disability v2.931 PIGC Rebecca Foulger Classified gene: PIGC as Amber List (moderate evidence)
Intellectual disability v2.931 PIGC Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber following external review by Zornitza Stark. Not yet associated with a disorder in OMIM, and two cases in the current literature (PMID:27694521).
Intellectual disability v2.931 PIGC Rebecca Foulger Gene: pigc has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.930 PIGC Rebecca Foulger commented on gene: PIGC
Intellectual disability v2.930 CACNA1B Louise Daugherty Classified gene: CACNA1B as Green List (high evidence)
Intellectual disability v2.930 CACNA1B Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.
Intellectual disability v2.930 CACNA1B Louise Daugherty Gene: cacna1b has been classified as Green List (High Evidence).
Intellectual disability v2.930 PIGC Rebecca Foulger Phenotypes for gene: PIGC were changed from Glycosylphosphatidylinositol biosynthesis defect 16 to Glycosylphosphatidylinositol biosynthesis defect 16, 617816
Early onset or syndromic epilepsy v1.96 CACNA1B Louise Daugherty Classified gene: CACNA1B as Green List (high evidence)
Early onset or syndromic epilepsy v1.96 CACNA1B Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.
Early onset or syndromic epilepsy v1.96 CACNA1B Louise Daugherty Gene: cacna1b has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.95 PIGC Rebecca Foulger Classified gene: PIGC as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.95 PIGC Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber following external review by Zornitza Stark. Not yet associated with a disorder in Gene2Phenotype, and currently only 2 families from one paper identified in the literature (PMID:27694521) for PIGC.
Early onset or syndromic epilepsy v1.95 PIGC Rebecca Foulger Gene: pigc has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.929 CACNA1B Louise Daugherty Added comment: Comment on phenotypes: added Progressive Epilepsy-Dyskinesia from PMID:30982612. gene-phenotype currently not listed in OMIM
Intellectual disability v2.929 CACNA1B Louise Daugherty Phenotypes for gene: CACNA1B were changed from Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement to Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia
Early onset or syndromic epilepsy v1.94 CACNA1B Louise Daugherty Added comment: Comment on phenotypes: added Progressive Epilepsy-Dyskinesia from PMID:30982612. gene-phenotype currently not listed in OMIM
Early onset or syndromic epilepsy v1.94 CACNA1B Louise Daugherty Phenotypes for gene: CACNA1B were changed from Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia to Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia
Early onset or syndromic epilepsy v1.93 PIGC Rebecca Foulger Phenotypes for gene: PIGC were changed from to Glycosylphosphatidylinositol biosynthesis defect 16, 617816
Early onset or syndromic epilepsy v1.92 PIGC Rebecca Foulger Mode of inheritance for gene: PIGC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.91 CACNA1B Louise Daugherty Phenotypes for gene: CACNA1B were changed from Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement to Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia
Intellectual disability v2.928 CACNA1B Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association
Intellectual disability v2.928 CACNA1B Louise Daugherty Publications for gene: CACNA1B were set to
Early onset or syndromic epilepsy v1.90 CACNA1B Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association
Early onset or syndromic epilepsy v1.90 CACNA1B Louise Daugherty Publications for gene: CACNA1B were set to
Early onset or syndromic epilepsy v1.89 PIGC Rebecca Foulger changed review comment from: PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from a consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.; to: PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.
Early onset or syndromic epilepsy v1.89 PIGC Rebecca Foulger changed review comment from: PMID:27694521: Edvardson et al. 201x studied 2 unrelated families (two siblings from a consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.; to: PMID:27694521: Edvardson et al. 2017 studied 2 unrelated families (two siblings from a consanguineous Moslem-Arab parents, and a son of unrelated Sephardic-Jewish parents) who suffered from global DD, ID and seizures. PIGC variants were found: homozygous p.L189W in one family, and compound het variant (L212P/R21X) in another.
Early onset or syndromic epilepsy v1.89 PIGC Rebecca Foulger commented on gene: PIGC
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger changed review comment from: Comment on list classification: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model. There is limited patient information because severe LOF alleles are incompatible with life.; to: Comment on list classification: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model (PMID:19640479). There is limited patient information because severe LOF alleles are incompatible with life.
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger Classified gene: KIAA1109 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger Added comment: Comment on list classification: Re-assessed gene:disease evidence based on 2019 paper (PMID:30906834). Kept rating as Amber awaiting further information: seizures present in 2 Lithuanian siblings (PMID:29290337) plus two African-American siblings (PMID:30906834). Plus Drosophila model. There is limited patient information because severe LOF alleles are incompatible with life.
Early onset or syndromic epilepsy v1.89 KIAA1109 Rebecca Foulger Gene: kiaa1109 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.116 HYAL1 Sarah Leigh Added comment: Comment on phenotypes: MPS IX, Natowicz (MPS IV, Morquio disease)
Undiagnosed metabolic disorders v1.116 HYAL1 Sarah Leigh Phenotypes for gene: HYAL1 were changed from MPS IX, Natowicz (MPS IV, Morquio disease); ?Mucopolysaccharidosis type IX, 601492 to ?Mucopolysaccharidosis type IX, 601492
Undiagnosed metabolic disorders v1.115 HYAL1 Sarah Leigh Publications for gene: HYAL1 were set to 27604308
Fetal anomalies v0.295 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to 30485398; 29290337
Fetal anomalies v0.294 KIAA1109 Rebecca Foulger Added comment: Comment on mode of pathogenicity: The Mode of pathogenicity recorded in Gene2Phenotype for the disorder 'Brain atrophy, Dandy Walker and Contractures' is: All missense/in frame. However, as summarised in PMID:29290337 (Gueneau et al., 2018),
case subjects compatible with life carry missense variants but many of the more severely affected cases harbor homozygous or compound het truncating alleles. Therefore changed the Mode of pathogenicity back to default so LOF variants are captured.
Fetal anomalies v0.294 KIAA1109 Rebecca Foulger Mode of pathogenicity for gene: KIAA1109 was changed from Other to None
Fetal anomalies v0.293 KIAA1109 Rebecca Foulger Classified gene: KIAA1109 as Green List (high evidence)
Fetal anomalies v0.293 KIAA1109 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green after agreement from Anna de Burca (Genomics England clinical team). KIAA1109 is Green on the 'Hydrocephalus' and 'Arthrogryposis' panels. Sufficient cases in OMIM to support association with Alkuraya-Kucinskas syndrome (MIM:617822) which includes arthrogryposis and brain abnormalities: severe cases are incompatible with life. Multiple ultrasounds abnormalities reported in PMIDs 30485398 and 29290337.
Fetal anomalies v0.293 KIAA1109 Rebecca Foulger Gene: kiaa1109 has been classified as Green List (High Evidence).
Fetal anomalies v0.292 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to 30485398
Fetal anomalies v0.291 KIAA1109 Rebecca Foulger Phenotypes for gene: KIAA1109 were changed from Brain atrophy, Dandy Walker and Contractures to Brain atrophy, Dandy Walker and Contractures; Alkuraya-Kucinskas syndrome, 617822
Fetal anomalies v0.290 KIAA1109 Rebecca Foulger commented on gene: KIAA1109: PMID:30485398: Filatova et al. 2019 report a Russian family with fetal anomalies detected upon ultrasound scans of three pregnancies. The first pregnancy resulted in a miscarriage. The second and third pregnancies were terminated because of ultrasound fetal abnormalities. In the third pregnancy, anomalies included bilateral ventriculomegaly, arthrogryposis (radial clubhand, bilateral clubfoot, flexed deformity of hip, knee and ankle joints), bilateral pyelectasis, increased thickness of the nuchal‐fold, hypoplastic and low set ears- Sanger sequencing revealed that the polymalformative fetus had compound heterozygous KIAA1109 variants. One of the dichorionic twins in the 4th pregnancy had similar phenotype and biallelic KIAA1109 variants (the healthy twin had only one variant c.1932‐3A>G).
Fetal anomalies v0.290 KIAA1109 Rebecca Foulger Mode of pathogenicity for gene: KIAA1109 was changed from to Other
Undiagnosed metabolic disorders v1.114 ARSG Sarah Leigh changed review comment from: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in a ; to: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in 5 affected members of 3 consanguineous Yemenite Jewish families (PMID 29300381).
Fetal anomalies v0.289 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to
Early onset or syndromic epilepsy v1.88 KIAA1109 Rebecca Foulger Phenotypes for gene: KIAA1109 were changed from Alkuraya-Kucinskas syndrome 617822 to Alkuraya-Kucinskas syndrome 617822; seizures
Undiagnosed metabolic disorders v1.114 ARSG Sarah Leigh Mode of inheritance for gene: ARSG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.113 ARSG Sarah Leigh Publications for gene: ARSG were set to 20679209; 25452429; 26975023; 29300381
Undiagnosed metabolic disorders v1.112 ARSG Sarah Leigh changed review comment from: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice; to: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in a
Early onset or syndromic epilepsy v1.87 KIAA1109 Rebecca Foulger Publications for gene: KIAA1109 were set to 29290337; 19640479
Early onset or syndromic epilepsy v1.86 KIAA1109 Rebecca Foulger commented on gene: KIAA1109
Undiagnosed metabolic disorders v1.112 ARSG Sarah Leigh Added comment: Comment on phenotypes: Including neuronal ceroid lipofuscinosis
Undiagnosed metabolic disorders v1.112 ARSG Sarah Leigh Phenotypes for gene: ARSG were changed from neuronal ceroid lipofuscinosis to Usher syndrome, type IV 618144
Lysosomal storage disorder v0.6 ARSG Sarah Leigh Added comment: Comment on phenotypes: Including of neuronal ceroid lipofuscinosis
Lysosomal storage disorder v0.6 ARSG Sarah Leigh Phenotypes for gene: ARSG were changed from to Usher syndrome, type IV 618144
Lysosomal storage disorder v0.5 ARSG Sarah Leigh Publications for gene: ARSG were set to
Early onset or syndromic epilepsy v1.86 EFHC1 Rebecca Foulger Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686; 28370826
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger commented on gene: EFHC1: PMID:29750216: Thounaojam et al., 2017 studied 63 Indian patients from 63 independent families with Juvenile myoclonic epilepsy (JME) and found 4 heterozygous coding variants (R221C, R260Q, R294H and R244STOP) and 1 homozygous and one heterozygous coding variant (R159W, which is considered a polymorphism). Lack of family samples meant the mode of inheritance couldn't be followed up.
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger commented on gene: EFHC1: PMID:31056551: Heyne et al., 2019 performed a large-scale analysis of previously-sequenced variants in individuals with a 'neurodevelopmental disorder with epilepsy. They show that EFHC1 showed equal frequencies of ultra-rare variants in cases and controls supporting the existing evidence that EFHC1 may not be truly associated with epilepsy.
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger changed review comment from: PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).; to: PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. All variants were missense. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger commented on gene: EFHC1
Familial hypercholesterolaemia v1.22 APOE Sarah Leigh Publications for gene: APOE were set to PMID: 23433584; 22949395; 26802169
Early onset or syndromic epilepsy v1.85 EFHC1 Rebecca Foulger Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomic Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876)

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomic Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Inherited white matter disorders v1.69 ISCA2 Ivone Leong Classified gene: ISCA2 as Green List (high evidence)
Inherited white matter disorders v1.69 ISCA2 Ivone Leong Added comment: Comment on list classification: Promoted from red to green, based on evidence provided by expert reviewer and also advice from the Genomics England Clinical team.
Inherited white matter disorders v1.69 ISCA2 Ivone Leong Gene: isca2 has been classified as Green List (High Evidence).
Inherited white matter disorders v1.68 ISCA2 Ivone Leong Phenotypes for gene: ISCA2 were changed from to Multiple mitochondrial dysfunctions syndrome 4, 616370
Inherited white matter disorders v1.67 ISCA2 Ivone Leong Publications for gene: ISCA2 were set to 27564080; 25558065; 25539947; 22323289
Intellectual disability v2.927 ISCA2 Ivone Leong Classified gene: ISCA2 as Amber List (moderate evidence)
Intellectual disability v2.927 ISCA2 Ivone Leong Added comment: Comment on list classification: After consulting with the Genomics England Clinical team it was decided to only promote this gene to amber as the clinical picture is more of a mitochondrial phenotype and is likely to be investigated that way.
Intellectual disability v2.927 ISCA2 Ivone Leong Gene: isca2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.926 CWC27 Ivone Leong Classified gene: CWC27 as Green List (high evidence)
Intellectual disability v2.926 CWC27 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. CWC27 is associated with a phenotype in OMIM and Gene2Phenotype. PMID: 28285769 reported on 7 unrelated families (10 affected individuals) with variants in this gene. 8/10 had neurological problems, which include ID, delayed walking, delayed speech or psychomotor retardation. Two cases (same family) are specified as moderate ID and they have indicated severe psychomotor retardation in others. After consulting the Genomics England Clinical Team, it was decided that there is enough evidence to promote this to green status.
Intellectual disability v2.926 CWC27 Ivone Leong Gene: cwc27 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.84 CUL4B Rebecca Foulger Classified gene: CUL4B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.84 CUL4B Rebecca Foulger Added comment: Comment on list classification: Added CUL4B to the panel and rated Amber awaiting further clinical review. Seizures are noted in the literature in >30% of patients- although there are sufficient unrelated cases, the seizure phenotype is not consistent. Plus some of the cases recorded as seizures refer to febrile seizures, which are out of scope of this panel (e.g. PMID:17236139), and detailed information on seizures is not provided in most papers.
Early onset or syndromic epilepsy v1.84 CUL4B Rebecca Foulger Gene: cul4b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:20014135: Isifor et al., 2010 report a de novo deletion of CUL4B in a boy with syndromic ID. Seizures were not reported.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:20002452: Badura-Stronka et al., 2010 report a CUL4B nonsense variant in 3 brothers with X-linked ID.
2 brothers had a single seizure, in the setting of infection. Therefore not appropriate in the context of this epilepsy panel.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger changed review comment from: PMID:17273978: Zou et al., 2007 analyse a previously reported (PMID:8135271) family (5 individuals) with X-linked ID and implicate p.R388X nonsense variant in CUL4B as the cause. 4/5 patients had seizures according to the summaries in PMID:20014135 and PMID:22182342; to: PMID:17273978: Zou et al., 2007 analyse a previously reported (PMID:8135271) family (5 individuals) with X-linked ID and implicate p.R388X nonsense variant in CUL4B as the cause. 4/5 patients had seizures according to the summaries in PMID:20014135 and PMID:22182342.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:17273978: Zou et al., 2007 analyse a previously reported (PMID:8135271) family (5 individuals) with X-linked ID and implicate p.R388X nonsense variant in CUL4B as the cause. 4/5 patients had seizures according to the summaries in PMID:20014135 and PMID:22182342
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:22182342: Ravn et al., 2012 report a monozygotic Danish twin pair with a CUL4B deletion. Seizures is reported in both patients but no further details on the seizures are given. Ravn et al also summarise previous studies and note seizues in 14/22 patients. However this includes the febrile seizures noted in PMID:17236139 (Tarpet et al 2007).
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:17236139: Tarpet et al., 2007 report CUL4B variants in 8/250 families with X-linked mental retardation. Segregation analysis is performed for all 8 families. Seizures (before age 2) reported in 8/11 affected males (Table 2). However the seizures are reported to be usually single febrile fits. The authors also note that further evidence is required to confirm that the missense variants are disease causing (e.g. in Family 432 it is possible that C638C>T (T213I) is a rare variant because ethically-matched controls were unavailable).
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: PMID:25385192: Vulto-van Silfhout et al, 2015 identified CUL4B variants in 8/407 families with X-linked mental retardation. Plus CUL4B variants in an additional 3 patients (2 families) with malformations of cortical development. Ten different variants were identified in the 10 families (5 truncating, 2 splice, 1 in-frame deletion, 1 in-frame duplication, 1 missense). Across the 10 families with CUL4B variants, 7/22 (32%) of the individuals had seizures, though the phenotype was not always consistent between family members: In both family 1 (N151) and family 5 (D173), 1 of 3 individuals had seizures. The authors note that previously 17/30 (57%) of individuals with CUL4B variants were reported to have seizures.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger commented on gene: CUL4B: Seizures listed amongst the phenotypes of MENTAL RETARDATION SYNDROMIC X-LINKED CABEZAS TYPE in Gene2Phenotype. Seizures (onset <2 years) listed amongst the phenotypes in OMIM for Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM:300354.
Early onset or syndromic epilepsy v1.83 CUL4B Rebecca Foulger Publications for gene: CUL4B were set to 25385192; 17236139
Early onset or syndromic epilepsy v1.82 CUL4B Rebecca Foulger gene: CUL4B was added
gene: CUL4B was added to Genetic epilepsy syndromes. Sources: NHS GMS,Literature
Mode of inheritance for gene: CUL4B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CUL4B were set to 25385192; 17236139
Phenotypes for gene: CUL4B were set to Mental retardation, X-linked, syndromic 15 (Cabezas type), 300354; seizures
Added comment: Added to Genetic epilepsy syndromes panel based on gene list submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Sources: NHS GMS, Literature
DDG2P v1.75 PCDH19 Rebecca Foulger Added comment: Comment on mode of inheritance: Note that the allelic requirement for PCDH19 in Gene2Phenotype is x-linked over-dominance. Note from Anna de Burca (Genomics England clinical team): PCDH19 only causes epilepsy in heterozygous females, and hemizygous males are unaffected. For the purposes of the pipeline, use 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease' to ensure that females with a variant are not missed.
DDG2P v1.75 PCDH19 Rebecca Foulger Mode of inheritance for gene: PCDH19 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v2.925 TRAPPC12 Louise Daugherty changed review comment from: Comment on list classification: Appropriate phenotype, sufficient cases due to on unpublished report all support gene-disease association and relevance to this panel to rate gene to Green.; to: Comment on list classification: Appropriate phenotype, sufficient cases due to an unpublished report that supports gene-disease association and relevance to this panel to rate gene from Red to Green.
Intellectual disability v2.925 SMARCD1 Ivone Leong Publications for gene: SMARCD1 were set to 26350204
Intellectual disability v2.924 TRAPPC12 Louise Daugherty Classified gene: TRAPPC12 as Green List (high evidence)
Intellectual disability v2.924 TRAPPC12 Louise Daugherty Added comment: Comment on list classification: Appropriate phenotype, sufficient cases due to on unpublished report all support gene-disease association and relevance to this panel to rate gene to Green.
Intellectual disability v2.924 TRAPPC12 Louise Daugherty Gene: trappc12 has been classified as Green List (High Evidence).
Intellectual disability v2.923 TRAPPC12 Louise Daugherty Phenotypes for gene: TRAPPC12 were changed from Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669 to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669; Developmental delay
Intellectual disability v2.922 TRAPPC12 Louise Daugherty Publications for gene: TRAPPC12 were set to 28777934
Intellectual disability v2.922 TRAPPC12 Louise Daugherty Phenotypes for gene: TRAPPC12 were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669
Intellectual disability v2.921 TRAPPC12 Louise Daugherty Publications for gene: TRAPPC12 were set to
Intellectual disability v2.921 TRAPPC12 Louise Daugherty Mode of inheritance for gene: TRAPPC12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.920 TRAPPC12 Louise Daugherty reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.920 PPP3CA Ivone Leong Classified gene: PPP3CA as Green List (high evidence)
Intellectual disability v2.920 PPP3CA Ivone Leong Added comment: Comment on list classification: Promoted from red to green. PPP3CA is associated with Epileptic encephalopathy, infantile or early childhood, 1 in OMIM and is probably associated with Severe Neurodevelopmental Disease with Seizures
Page navigation in Gene2Phenotype. PMID: 28942967 reported on 6 unrelated individuals from different ethnic backgrounds who have different PPP3CA variants (missense and nonsense) who have severe ID. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.920 PPP3CA Ivone Leong Gene: ppp3ca has been classified as Green List (High Evidence).
DDG2P v1.74 MN1 Rebecca Foulger commented on gene: MN1
DDG2P v1.74 EIF3F Rebecca Foulger commented on gene: EIF3F
DDG2P v1.74 BRD4 Rebecca Foulger commented on gene: BRD4
DDG2P v1.74 PCDH19 Rebecca Foulger Added comment: Comment on mode of inheritance: Changed Mode of Inheritance from 'x-linked over dominance' to a PanelApp standardised MOI term.
DDG2P v1.74 PCDH19 Rebecca Foulger Mode of inheritance for gene: PCDH19 was changed from x-linked over-dominance to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v2.919 PPP3CA Ivone Leong Phenotypes for gene: PPP3CA were changed from Epileptic encephalopathy, infantile or early childhood, 1 to Epileptic encephalopathy, infantile or early childhood, 1, 617711
DDG2P v1.73 MN1 Rebecca Foulger gene: MN1 was added
gene: MN1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MN1 were set to 21242494
Phenotypes for gene: MN1 were set to MN1 C-terminal truncation syndrome
DDG2P v1.73 EIF3F Rebecca Foulger gene: EIF3F was added
gene: EIF3F was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 30409806
Phenotypes for gene: EIF3F were set to EIF3F related developmental disorder
DDG2P v1.73 BRD4 Rebecca Foulger gene: BRD4 was added
gene: BRD4 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BRD4 were set to 29379197; 30302754
Phenotypes for gene: BRD4 were set to CORNELIA DE LANGE-LIKE SYNDROME
DDG2P v1.72 RAD51 Rebecca Foulger Classified gene: RAD51 as Red List (low evidence)
DDG2P v1.72 RAD51 Rebecca Foulger Added comment: Comment on list classification: Changed rating from Amber to Red to reflect a change in DD-G2P Disease confidence from probable to possible in June 2019. Disease remains as: MIRROR MOVEMENTS 2. Mode of inheritance remains as: monoallelic. Mode of pathogenicity remains as: loss of function.
DDG2P v1.72 RAD51 Rebecca Foulger Gene: rad51 has been classified as Red List (Low Evidence).
DDG2P v1.71 CHD3 Rebecca Foulger Phenotypes for gene: CHD3 were changed from Apraxia of speech to Macrocephaly and impaired speech and language
DDG2P v1.70 CHD3 Rebecca Foulger Added comment: Comment on publications: Added PMID:30397230 based on June 2019 DD-G2P update for CHD3. Removed PMID:29463886 as it is no longer listed as a reference in DD-G2P for CHD3.
DDG2P v1.70 CHD3 Rebecca Foulger Publications for gene: CHD3 were set to 29463886
DDG2P v1.69 CHD3 Rebecca Foulger Added comment: Comment on phenotypes: Replaced phenotype 'Apraxia of speech' with 'Macrocephaly and impaired speech and language' to reflect June 2019 DD-G2P update for CHD3. Disease confidence rating remains as: probable. Mode of inheritance remains as: monoallelic. Mode of pathogenicity remains as: all missense/in frame.
DDG2P v1.69 CHD3 Rebecca Foulger Phenotypes for gene: CHD3 were changed from Apraxia of speech to Apraxia of speech
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Classified gene: NUP133 as Green List (high evidence)
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Added comment: Comment on list classification: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of Galloway-Mowat syndrome. Sufficient cases to rate green.
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Gene: nup133 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.214 WDR73 Eleanor Williams Mode of inheritance for gene: WDR73 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Classified gene: WDR73 as Green List (high evidence)
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Added comment: Comment on list classification: Sufficient cases and GMS renal specialist test group decided Galloway-Mowat syndrome is appropriate for this panel
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Gene: wdr73 has been classified as Green List (High Evidence).
IUGR and IGF abnormalities v1.26 AMMECR1 Julia Baptista changed review comment from: Basel-Vanagaite et al reported a boy with short stature (−3SD), low weight(−4SD), normal OFC (+1SD) and dysmorphic features (PMID: 28089922).

Maternal half-brothers reported by Andreoletti et al. (2017) also had short stature (below the 0.4th centile) and midface hypoplasia.

Short stature was also reported by Moyses-Oliveira et al in patients with loss-of-function AMMECR1 alleles due to nonsense variants, gene deletion and a translocation.; to: Basel-Vanagaite et al reported a boy with short stature (−3SD), low weight(−4SD), normal OFC (+1SD) and dysmorphic features (PMID: 28089922).

Maternal half-brothers reported by Andreoletti et al. (2017) also had short stature (below the 0.4th centile) and midface hypoplasia.

Short stature was also reported by Moyses-Oliveira et al in patients with loss-of-function AMMECR1 alleles due to nonsense variants, gene deletion and a translocation. (PMID: 29193635)
IUGR and IGF abnormalities v1.26 AMMECR1 Julia Baptista edited their review of gene: AMMECR1: Added comment: Basel-Vanagaite et al reported a boy with short stature (−3SD), low weight(−4SD), normal OFC (+1SD) and dysmorphic features (PMID: 28089922).

Maternal half-brothers reported by Andreoletti et al. (2017) also had short stature (below the 0.4th centile) and midface hypoplasia.

Short stature was also reported by Moyses-Oliveira et al in patients with loss-of-function AMMECR1 alleles due to nonsense variants, gene deletion and a translocation.; Changed publications: PMID: 29193635, 28089922, 27811305; Changed phenotypes: Short stature, midface hypoplasia, hearing impairment, elliptocytosis, nephrocalcinosis
IUGR and IGF abnormalities v1.26 AMMECR1 Julia Baptista gene: AMMECR1 was added
gene: AMMECR1 was added to IUGR and IGF abnormalities. Sources: Literature
Mode of inheritance for gene: AMMECR1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AMMECR1 were set to Short stature; Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
Review for gene: AMMECR1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability v2.918 PPP1R15B Ivone Leong Classified gene: PPP1R15B as Green List (high evidence)
Intellectual disability v2.918 PPP1R15B Ivone Leong Added comment: Comment on list classification: Promoted from red to green. PPP1R15B is associated with a phenotype in OMIM and possibly associated with a phenotype in Gene2Phenotype. PMID: 26159176, 26307080 reported on 2 unrelated patients (Canadian, Algerian) who have the same missense variant in the PPP1R15B gene. Both patients have ID. PMID:27640355 reported on another case where the patient was compound heterozygous for 2 different variants (1 frameshift and 1 nonsense). The patient also had ID. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.918 PPP1R15B Ivone Leong Gene: ppp1r15b has been classified as Green List (High Evidence).
Intellectual disability v2.917 PPP1R15B Ivone Leong Phenotypes for gene: PPP1R15B were changed from Microcephaly, short stature, and impaired glucose metabolism 2 to Microcephaly, short stature, and impaired glucose metabolism 2, 616817
Intellectual disability v2.916 PPP1R15B Ivone Leong Publications for gene: PPP1R15B were set to 26159176, 26307080, 27640355
Intellectual disability v2.915 PIGW Ivone Leong Classified gene: PIGW as Green List (high evidence)
Intellectual disability v2.915 PIGW Ivone Leong Added comment: Comment on list classification: Promoted from red to green, based the expert reviews and the evidence that was provided.
Intellectual disability v2.915 PIGW Ivone Leong Gene: pigw has been classified as Green List (High Evidence).
Intellectual disability v2.914 PIGW Ivone Leong Phenotypes for gene: PIGW were changed from Glycosylphosphatidylinositol biosynthesis defect 11 to Glycosylphosphatidylinositol biosynthesis defect 11, 616025
Intellectual disability v2.913 PIGW Ivone Leong Publications for gene: PIGW were set to 24367057, 27626616, 27626616
Intellectual disability v2.912 NDUFAF5 Ivone Leong Phenotypes for gene: NDUFAF5 were changed from Mitochondrial complex 1 deficiency to Mitochondrial complex 1 deficiency, 618238
Intellectual disability v2.911 MTFMT Ivone Leong Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15 to Combined oxidative phosphorylation deficiency 15, 614947
Intellectual disability v2.910 NDUFAF5 Ivone Leong Publications for gene: NDUFAF5 were set to 19542079, 21607760, 18940309
Intellectual disability v2.909 MTFMT Ivone Leong Classified gene: MTFMT as Green List (high evidence)
Intellectual disability v2.909 MTFMT Ivone Leong Added comment: Comment on list classification: Promoted from red to green. MTFMT is associated with a phenotype in OMIM but not in Gene2Phenotype. There are >3 unrelated cases of patients who have different variants in this gene who have ID or developmental delay. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.909 MTFMT Ivone Leong Gene: mtfmt has been classified as Green List (High Evidence).
Intellectual disability v2.908 MTFMT Ivone Leong Publications for gene: MTFMT were set to 24461907; 23499752
Intellectual disability v2.907 MTFMT Ivone Leong Publications for gene: MTFMT were set to 24461907; 23499752; 24461907
Intellectual disability v2.906 MTFMT Ivone Leong Publications for gene: MTFMT were set to 24461907, 23499752, 24461907
Intellectual disability v2.905 KMT5B Ivone Leong Publications for gene: KMT5B were set to 29276005, 28191889, 25363768
Early onset or syndromic epilepsy v1.81 CSNK2A1 Rebecca Foulger Classified gene: CSNK2A1 as Red List (low evidence)
Early onset or syndromic epilepsy v1.81 CSNK2A1 Rebecca Foulger Added comment: Comment on list classification: Rated CSNK2A1 as Red based on 1 paper (PMID:30655572) with 2 unrelated Japanese patients and de novo variants. Functional studies were not performed, and the seizures (and other features) were variable between the patients.
Early onset or syndromic epilepsy v1.81 CSNK2A1 Rebecca Foulger Gene: csnk2a1 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v1.80 CSNK2A1 Rebecca Foulger gene: CSNK2A1 was added
gene: CSNK2A1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSNK2A1 were set to 30655572
Phenotypes for gene: CSNK2A1 were set to seizures; Okur-Chung neurodevelopmental syndrome, 617062; CSNK2A1 syndrome
Review for gene: CSNK2A1 was set to AMBER
Added comment: Added CSNK2A1 to the epilepsy panel based on PMID:30655572. Nakashima et al, 2019 describe 4 patients with DD and seizures. Two of the patients (both Japanese) had de novo variants in CSNK2A1: c.593A>G, p.Lys198Arg in Patient 1, c.571C>T, p.Arg191* in Patient 2. Although both shared global DD and seizures, patient 1 showed later onset (4 yrs old) seizures which were less frequent. Additional features in Patient 1 include facial dysmorphisms, short stature and muscle weakness. Patient 2 had a more severe phenotype with seizures starting in the early infantile stage (5 months) with acute encephalopathy and death age 1 yr, 7 months. Note that Patient 1 had 3 candidate de novo deleterious variants (ATAD2B, TOPORS, CSNK2A1): ACMG variant guidelines were used to evaluate the pathogenicity of the variants. ATAD2B and TOPORS variants were likely pathogenic, and CSNK2A1 variant was pathogenic. In Patient 2, no further likely de novo variants were found.
Sources: Literature
Early onset or syndromic epilepsy v1.79 CSNK2B Rebecca Foulger Classified gene: CSNK2B as Green List (high evidence)
Early onset or syndromic epilepsy v1.79 CSNK2B Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on recent 2019 paper, PMID:30655572, which reports two further unrelated cases (Japanese and Malaysian) of de novo CSNK2B variants in patients with epilepsy. Although CSNK2B is still not associated with a disorder in OMIM or Gene2Phenotype, this takes the count from two to four cases (from 3 different papers) and is therefore sufficient for a Green rating on this panel.
Early onset or syndromic epilepsy v1.79 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.78 CSNK2B Rebecca Foulger commented on gene: CSNK2B: PMID:30655572: Nakashima et al, 2019 describe 4 patients with ID, DD and seizures. Two of the patients had variants in CSNK2B: c.533_534insGT, p.(Pro179Tyrfs*49) in Malaysian Patient 3, and c.494A>G, p.(His165Arg) in Japanese Patient 4. Both had seizures within 2 months of age. Both variants occurred de novo. In each patient, only 1 likely candidate variant was proposed. Functional assays suggested that Pro179Tyrfs*49 mutant protein was produced but showed disrupted interaction with CSNK2A1.
Intellectual disability v2.904 CSNK2B Rebecca Foulger Deleted their comment
Intellectual disability v2.904 KLHL7 Ivone Leong Classified gene: KLHL7 as Green List (high evidence)
Intellectual disability v2.904 KLHL7 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. KLHL7 is associated with Cold-induced sweating syndrome 3 (OMIM: 617055) in OMIM and Gene2Phenotype, but not BOS-like phenotype. There are 7 unrelated cases (PMID: 29074562, 30300710) from 5 unrelated families with affected individuals with BOS-like phenotype, global developmental delay and IUGR, who have different variants (nonsense, splicing and small deletions) in the KLHL7 gene.
There is also several cases (PMID: 30142437, being one reported case) of patients with variants in KLHL7 who have phenotypes that overlap Cold-induced sweating syndrome 3 and BOS-like phenotype. This patient also had global developmental delay and a variant different from those reported in PMID: 29074562, 30300710.

Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.904 KLHL7 Ivone Leong Gene: klhl7 has been classified as Green List (High Evidence).
Intellectual disability v2.903 CSNK2B Rebecca Foulger commented on gene: CSNK2B: PMID:30655572: Nakashima et al, 2019 describe 4 patients with ID, DD and seizures. Two of the patients had variants in CSNK2B: c.533_534insGT, p.(Pro179Tyrfs*49) in Malaysian Patient 3, and c.494A>G, p.(His165Arg) in Japanese Patient 4. Both had seizures within 2 months of age. Both variants occurred de novo. In each patient, only 1 likely candidate variant was proposed. Functional assays suggested that Pro179Tyrfs*49 mutant protein was produced but showed disrupted interaction with CSNK2A1.
Intellectual disability v2.903 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to 28585349; 28762608
Intellectual disability v2.902 KLHL7 Ivone Leong Publications for gene: KLHL7 were set to 29074562
Early onset or syndromic epilepsy v1.78 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to 28762608; 28585349; 27094248
Primary lymphoedema v1.81 SPRED1 Sarah Leigh Publications for gene: SPRED1 were set to
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Classified gene: SPRED1 as Green List (high evidence)
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Gene: spred1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.79 SOS2 Sarah Leigh Publications for gene: SOS2 were set to
Primary lymphoedema v1.78 SOS2 Sarah Leigh Classified gene: SOS2 as Green List (high evidence)
Primary lymphoedema v1.78 SOS2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.78 SOS2 Sarah Leigh Gene: sos2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.77 SOS1 Sarah Leigh Publications for gene: SOS1 were set to
Primary lymphoedema v1.76 SOS1 Sarah Leigh Classified gene: SOS1 as Green List (high evidence)
Primary lymphoedema v1.76 SOS1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.76 SOS1 Sarah Leigh Gene: sos1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.75 SHOC2 Sarah Leigh Publications for gene: SHOC2 were set to
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Classified gene: SHOC2 as Green List (high evidence)
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Gene: shoc2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.73 RIT1 Sarah Leigh Publications for gene: RIT1 were set to
Primary lymphoedema v1.72 RIT1 Sarah Leigh Classified gene: RIT1 as Green List (high evidence)
Primary lymphoedema v1.72 RIT1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.72 RIT1 Sarah Leigh Gene: rit1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.71 RAF1 Sarah Leigh Publications for gene: RAF1 were set to
Primary lymphoedema v1.70 RAF1 Sarah Leigh Classified gene: RAF1 as Green List (high evidence)
Primary lymphoedema v1.70 RAF1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.70 RAF1 Sarah Leigh Gene: raf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.69 PTPN11 Sarah Leigh Publications for gene: PTPN11 were set to
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Classified gene: PTPN11 as Green List (high evidence)
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Gene: ptpn11 has been classified as Green List (High Evidence).
Primary lymphoedema v1.67 PPP1CB Sarah Leigh Publications for gene: PPP1CB were set to
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Classified gene: PPP1CB as Green List (high evidence)
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Gene: ppp1cb has been classified as Green List (High Evidence).
Primary lymphoedema v1.65 NRAS Sarah Leigh Publications for gene: NRAS were set to
Primary lymphoedema v1.64 NRAS Sarah Leigh Classified gene: NRAS as Green List (high evidence)
Primary lymphoedema v1.64 NRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.64 NRAS Sarah Leigh Gene: nras has been classified as Green List (High Evidence).
Primary lymphoedema v1.63 NF1 Sarah Leigh Classified gene: NF1 as Green List (high evidence)
Primary lymphoedema v1.63 NF1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.63 NF1 Sarah Leigh Gene: nf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.62 NF1 Sarah Leigh Publications for gene: NF1 were set to
Primary lymphoedema v1.61 NF1 Sarah Leigh Classified gene: NF1 as Green List (high evidence)
Primary lymphoedema v1.61 NF1 Sarah Leigh Gene: nf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.60 MAP2K2 Sarah Leigh Publications for gene: MAP2K2 were set to
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Classified gene: MAP2K2 as Green List (high evidence)
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Gene: map2k2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.58 MAP2K1 Sarah Leigh Publications for gene: MAP2K1 were set to
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Classified gene: MAP2K1 as Green List (high evidence)
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Gene: map2k1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.56 LZTR1 Sarah Leigh Publications for gene: LZTR1 were set to
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Classified gene: LZTR1 as Green List (high evidence)
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Gene: lztr1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.54 KRAS Sarah Leigh Publications for gene: KRAS were set to
Primary lymphoedema v1.53 KRAS Sarah Leigh Classified gene: KRAS as Green List (high evidence)
Primary lymphoedema v1.53 KRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.53 KRAS Sarah Leigh Gene: kras has been classified as Green List (High Evidence).
Primary lymphoedema v1.52 HRAS Sarah Leigh Publications for gene: HRAS were set to
Primary lymphoedema v1.51 HRAS Sarah Leigh Classified gene: HRAS as Green List (high evidence)
Primary lymphoedema v1.51 HRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.51 HRAS Sarah Leigh Gene: hras has been classified as Green List (High Evidence).
Primary lymphoedema v1.50 CBL Sarah Leigh Classified gene: CBL as Green List (high evidence)
Primary lymphoedema v1.50 CBL Sarah Leigh Gene: cbl has been classified as Green List (High Evidence).
Primary lymphoedema v1.49 CBL Sarah Leigh Publications for gene: CBL were set to
Primary lymphoedema v1.48 CBL Sarah Leigh Classified gene: CBL as Red List (low evidence)
Primary lymphoedema v1.48 CBL Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.48 CBL Sarah Leigh Gene: cbl has been classified as Red List (Low Evidence).
Primary lymphoedema v1.47 BRAF Sarah Leigh Classified gene: BRAF as Green List (high evidence)
Primary lymphoedema v1.47 BRAF Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.47 BRAF Sarah Leigh Gene: braf has been classified as Green List (High Evidence).
Primary lymphoedema v1.46 BRAF Sarah Leigh Publications for gene: BRAF were set to
Primary lymphoedema v1.45 SPRED1 Sahar Mansour reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17704776, 19366998, 19443465, 21649642, 21548021; Phenotypes: Legius syndrome 611431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SOS2 Sahar Mansour reviewed gene: SOS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 25795793, 26173643; Phenotypes: Noonan syndrome 9 616559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SOS1 Sahar Mansour reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19438935, 17143285, 17143282, 17586837; Phenotypes: Noonan syndrome 4 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SHOC2 Sahar Mansour reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19684605, 22528146, 23918763; Phenotypes: Noonan-like syndrome with loose anagen hair 607721; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 RIT1 Sahar Mansour reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23791108, 25124994, 24939608; Phenotypes: Noonan syndrome 8 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 RAF1 Sahar Mansour reviewed gene: RAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17603483, 17603482; Phenotypes: LEOPARD syndrome 2 611554, Noonan syndrome 5 611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 PTPN11 Sahar Mansour reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: ; Publications: 17603483, 11704759, 12529711, 12634870, 15384080, 15240615, 16263833, 17497712, 18678287; Phenotypes: LEOPARD syndrome 1 151100, Noonan syndrome 1 163950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 PPP1CB Sahar Mansour reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: ; Publications: 27264673, 28211982, 27681385; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 NRAS Sahar Mansour reviewed gene: NRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 19966803, 19775298; Phenotypes: Noonan syndrome 6 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 NF1 Sahar Mansour reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16380919, 19845691, 12707950; Phenotypes: Neurofibromatosis-Noonan syndrome 601321, Neurofibromatosis, type 1 162200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 MAP2K2 Sahar Mansour reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583, 23379592; Phenotypes: Cardiofaciocutaneous syndrome 4 615280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 MAP2K1 Sahar Mansour reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583, 23321623; Phenotypes: Cardiofaciocutaneous syndrome 3 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 LZTR1 Sahar Mansour reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25795793, 29469822; Phenotypes: Noonan syndrome 10 616564 , Schwannomatosis-2, susceptibility to 615670; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.45 KRAS Sahar Mansour reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583; Phenotypes: Noonan syndrome 3 609942, Cardiofaciocutaneous syndrome 2 615278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 HRAS Sahar Mansour reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 16170316, 16969868, 16443854, 21396583; Phenotypes: Costello syndrome 218040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 CBL Sahar Mansour reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: ; Publications: 20619386, 20543203, 19571318; Phenotypes: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 BRAF Sahar Mansour reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: ; Publications: 19206169, 21396583; Phenotypes: LEOPARD syndrome 3 613707, Cardiofaciocutaneous syndrome 115150, Noonan syndrome 7 613706; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.44 SPRED1 Sarah Leigh gene: SPRED1 was added
gene: SPRED1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SPRED1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SPRED1 were set to Legius syndrome 611431
Primary lymphoedema v1.44 SOS2 Sarah Leigh gene: SOS2 was added
gene: SOS2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SOS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOS2 were set to Noonan syndrome 9 616559
Mode of pathogenicity for gene: SOS2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 SOS1 Sarah Leigh gene: SOS1 was added
gene: SOS1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOS1 were set to Noonan syndrome 4 610733
Mode of pathogenicity for gene: SOS1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 SHOC2 Sarah Leigh gene: SHOC2 was added
gene: SHOC2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SHOC2 were set to Noonan-like syndrome with loose anagen hair 607721
Primary lymphoedema v1.44 RIT1 Sarah Leigh gene: RIT1 was added
gene: RIT1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: RIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RIT1 were set to Noonan syndrome 8 615355
Mode of pathogenicity for gene: RIT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 RAF1 Sarah Leigh gene: RAF1 was added
gene: RAF1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RAF1 were set to Noonan syndrome 5 611553; LEOPARD syndrome 2 611554
Mode of pathogenicity for gene: RAF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 PTPN11 Sarah Leigh gene: PTPN11 was added
gene: PTPN11 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PTPN11 were set to Noonan syndrome 1 163950; LEOPARD syndrome 1 151100
Mode of pathogenicity for gene: PTPN11 was set to Other - please provide details in the comments
Primary lymphoedema v1.44 PPP1CB Sarah Leigh gene: PPP1CB was added
gene: PPP1CB was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2 617506
Primary lymphoedema v1.44 NRAS Sarah Leigh gene: NRAS was added
gene: NRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NRAS were set to Noonan syndrome 6 613224
Mode of pathogenicity for gene: NRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 NF1 Sarah Leigh gene: NF1 was added
gene: NF1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NF1 were set to Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis, type 1 162200
Primary lymphoedema v1.44 MAP2K2 Sarah Leigh gene: MAP2K2 was added
gene: MAP2K2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: MAP2K2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MAP2K2 were set to Cardiofaciocutaneous syndrome 4 615280
Mode of pathogenicity for gene: MAP2K2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 MAP2K1 Sarah Leigh gene: MAP2K1 was added
gene: MAP2K1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome 3 615279
Mode of pathogenicity for gene: MAP2K1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 LZTR1 Sarah Leigh gene: LZTR1 was added
gene: LZTR1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LZTR1 were set to Schwannomatosis-2, susceptibility to 615670; Noonan syndrome 10 616564
Primary lymphoedema v1.44 KRAS Sarah Leigh gene: KRAS was added
gene: KRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KRAS were set to Noonan syndrome 3 609942; Cardiofaciocutaneous syndrome 2 615278
Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 HRAS Sarah Leigh gene: HRAS was added
gene: HRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HRAS were set to Costello syndrome 218040
Mode of pathogenicity for gene: HRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 CBL Sarah Leigh gene: CBL was added
gene: CBL was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CBL were set to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 BRAF Sarah Leigh gene: BRAF was added
gene: BRAF was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BRAF were set to LEOPARD syndrome 3 613707; Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150
Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Intellectual disability v2.901 TCF20 Eleanor Williams Added comment: Comment on phenotypes: Updated as phenotype added to OMIM in May 2019
Intellectual disability v2.901 TCF20 Eleanor Williams Phenotypes for gene: TCF20 were changed from TCF20 syndrome; Intellectual disability; developmental delay to TCF20 syndrome; Intellectual disability; developmental delay; Developmental delay with variable intellectual impairment and behavioral abnormalities 618430
Fetal anomalies v0.288 TCF20 Eleanor Williams Added comment: Comment on phenotypes: updated as phenotype added to OMIM in May 2019
Fetal anomalies v0.288 TCF20 Eleanor Williams Phenotypes for gene: TCF20 were changed from TCF20 syndrome to TCF20 syndrome; Developmental delay with variable intellectual impairment and behavioral abnormalities 618430
Possible mitochondrial disorder - nuclear genes v0.204 SLC25A42 Eleanor Williams Added comment: Comment on phenotypes: Updated as phenotype added to OMIM in May 2019.
Possible mitochondrial disorder - nuclear genes v0.204 SLC25A42 Eleanor Williams Phenotypes for gene: SLC25A42 were changed from No OMIM phenotype to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression, 618416
Adult onset neurodegenerative disorder v1.49 ATXN7 Louise Daugherty changed review comment from: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Neurodegenerative disorders - adult onset panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATXN7_CAG and not the gene entity, as there are no SNVsfor this gene being associated to the disorder, this gene is rated RED.; to: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Hereditary ataxia panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATXN7_CAG and not the gene entity, but this needs to be checked during the Neurology test Group call July 2019
Possible mitochondrial disorder - nuclear genes v0.203 PARS2 Eleanor Williams Added comment: Comment on phenotypes: Phenotype added to OMIM in May 2019
Possible mitochondrial disorder - nuclear genes v0.203 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Infantile-onset encephalopathy; Alpers syndrome; Infantile-onset neurodegenerative disorder to Infantile-onset encephalopathy; Alpers syndrome; Infantile-onset neurodegenerative disorder; Epileptic encephalopathy, early infantile, 75, 61843
Mitochondrial disorders v1.401 PARS2 Eleanor Williams Added comment: Comment on phenotypes: Phenotype added to OMIM in May 2019
Mitochondrial disorders v1.401 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome. to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome; Epileptic encephalopathy, early infantile, 75, 618437
Hereditary ataxia with onset in adulthood v1.174 MAPK8IP3 Eleanor Williams commented on gene: MAPK8IP3
Hereditary ataxia with onset in adulthood v1.174 MAPK8IP3 Eleanor Williams Phenotypes for gene: MAPK8IP3 were changed from Intellectual Disability with variable brain anomalies to Intellectual Disability with variable brain anomalies; Neurodevelopmental disorder with or without variable brain abnormalities, 618443
Adult onset neurodegenerative disorder v1.49 ATXN7 Louise Daugherty commented on gene: ATXN7: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Neurodegenerative disorders - adult onset panel. The GREEN review from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) is likely to relate to the STR ATXN7_CAG and not the gene entity, as there are no SNVsfor this gene being associated to the disorder, this gene is rated RED.
Intellectual disability v2.900 KIF14 Ivone Leong Classified gene: KIF14 as Green List (high evidence)
Intellectual disability v2.900 KIF14 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. KIF14 is associated with a phenotype in OMIM but not in Gene2Phenotype. PMID: 29343805, 28892560 reported on 7 unrelated families with affected members who have moderate to severe ID and have different variants in KIF14. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.900 KIF14 Ivone Leong Gene: kif14 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.77 CNPY3 Rebecca Foulger Classified gene: CNPY3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.77 CNPY3 Rebecca Foulger Added comment: Comment on list classification: Re-reviewed gene:disease association for CNPY3 during curation of GMS panel. Amber rating is still appropriate: Probable Disease confidence rating in DD-G2P for EARLY ONSET EPILEPTIC ENCEPHALOPATHY, and literature evidence remains at 3 patients from 2 unrelated families from one paper (PMID:29394991) with limited segregation data from one of the families.
Early onset or syndromic epilepsy v1.77 CNPY3 Rebecca Foulger Gene: cnpy3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.899 KIF14 Ivone Leong Publications for gene: KIF14 were set to 29343805, 28892560
Early onset or syndromic epilepsy v1.76 CNPY3 Rebecca Foulger commented on gene: CNPY3
Intellectual disability v2.898 MAPK8IP3 Eleanor Williams Added comment: Comment on phenotypes: OMIM phenotype recently added to OMIM
Intellectual disability v2.898 MAPK8IP3 Eleanor Williams Phenotypes for gene: MAPK8IP3 were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; No OMIM number to Abnormal muscle tone; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Neurodevelopmental disorder with or without variable brain abnormalities, 618443
Early onset or syndromic epilepsy v1.76 ASAH1 Rebecca Foulger Publications for gene: ASAH1 were set to 29169047; 22703880; 24164096; 30291339; 27026573
Early onset or syndromic epilepsy v1.75 ASAH1 Rebecca Foulger Classified gene: ASAH1 as Green List (high evidence)
Early onset or syndromic epilepsy v1.75 ASAH1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green. Confirmed Disease confidence rating in Gene2Phenotype for SPINAL MUSCULAR ATROPHY ASSOCIATED WITH PROGRESSIVE MYOCLONIC EPILEPSY. Relevant disorder in OMIM (Spinal muscular atrophy with progressive myoclonic epilepsy, 159950). Although the three families reported in PMID:22703880 share a haplotype suggesting Founder effect, there are sufficient additional papers reporting cases with additional variants. Note that although most individuals report muscle weakness followed by seizures, PMIDs 27026573 and 30291339 report muscle weakness WITHOUT epilepsy, and PMID:24164096 also report a case with seizures without muscle weakness- there is therefore some heterogeneity in the phenotype. On balance there are plenty of literature reports of seizures in patients with biallelic ASAH1 variants for inclusion on this panel.
Early onset or syndromic epilepsy v1.75 ASAH1 Rebecca Foulger Gene: asah1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger commented on gene: ASAH1: Additional cases of seizures associated with SMA were reported in papers including PMIDs 27723502, 26526000, 25847462, 25578555, 31216804.
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:27723502 (Oguz et al, 2016) report eyelid myoclonic status epilepticus as an unusual manifestation of SMA-PME in a Turkish girl of consanguineous parents. Ambulatory problems were noted age 4. Generalized seizures developed later.
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:29169047: Yidiz et al (2018) report a 13.5 yr old girl with SMA-PME. She was the 8th child born of consanguineous parents. She presented with progressive muscle weakiness age 10, tremor, seizure (generalized epilepsy) and decreased cognitive functions. Screening revelead homozygous missense variant c.173C>T (T58M). The parents or siblings were not tested.
Intellectual disability v2.897 KIF14 Ivone Leong Phenotypes for gene: KIF14 were changed from Microcephaly 20, primary, autosomal recessive to Microcephaly 20, primary, autosomal recessive, 617914
Intellectual disability v2.896 KCTD3 Ivone Leong Publications for gene: KCTD3 were set to 29406573, 27848944, 25558065
Intellectual disability v2.895 KCTD3 Ivone Leong Phenotypes for gene: KCTD3 were changed from to Epilepsy and global developmental delay
Intellectual disability v2.894 KCTD3 Ivone Leong Classified gene: KCTD3 as Green List (high evidence)
Intellectual disability v2.894 KCTD3 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. No phenotypes are associated with this gene OMIM or Gene2Phenotype.
One study (PMID: 29406573) reported different variants in KCTD3 for 7 probands from 4 consanguineous families who all have epilepsy and global developmental disability. The families are from the same geographical location. The study did show that the variants segregated with the phenotype. Two other large (PMID: 27848944, 25558065) screening studies reported 2 probands with the same frameshift KCTD3 variant who have epilepsy and global developmental disability. This frameshift variant was also found in one of the probands in PMID: 29406573 article.
Intellectual disability v2.894 KCTD3 Ivone Leong Gene: kctd3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger changed review comment from: PMID:30291339: Ame van der Beek et al (2019) report an additional case of a mild SMA phenotype with NO myoclonic epilepsy due to variants in ASAH1. Ambulatory problems of the 24 year old female began around age 8 years.; to: PMID:30291339: Ame van der Beek et al (2019) report an additional case of a mild SMA phenotype with NO myoclonic epilepsy due to variants in ASAH1. She carried two novel ASAH1 variants (Pro26Arg and c.125+1G>A splice variant leading to an unstable transcript lacking exon 2. Segregation analysis confirmed the parental inheritance and acid ceramidase activity was deficient in functional tests.
Early onset or syndromic epilepsy v1.74 ASAH1 Rebecca Foulger Publications for gene: ASAH1 were set to 29169047; 22703880; 24164096
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:30291339: Ame van der Beek et al (2019) report an additional case of a mild SMA phenotype with NO myoclonic epilepsy due to variants in ASAH1. Ambulatory problems of the 24 year old female began around age 8 years.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:27026573: Filosto et al., 2016 studied 2 subjects: a 30yr old pregnant woman and her 17 year old sister affected with slowly progressive SMA since childhood but in the ABSENCE of siezures. Both subjects had a homozygous c.124A>G (T42A) variant in ASAH1.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1: PMID:24164096: In a girl who presented with absence and atonic seizures age 10, Dyment et al. (2014) identified compound heterozygous mutations in the ASAH1 gene: c.850G>T (G284X) and c.456A>C. Each parent was found to carry one of the variants. Although c.456A>C is predicted to encode a Lys152Asn substitution, it is 2bp away from a splice donor site and fibroblast assays showed an absence of exon 6, suggesting abberant splicing. Note that the patient harboured several hundred rare variants with at least two rare non-synonymous variants within the coding sequence of 4 genes (ASAH1, OC90, CACNA1C and LAMA5) though CACNA1C and OC90 were ruled out because the variants were found to be inherited from a single parent. Unlike the cases from PMID:22703880, this patient presented with seizures as the first symptom, and displayed no significant muscle weakness.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger commented on gene: ASAH1
Intellectual disability v2.893 ISCA2 Ivone Leong Tag founder-effect tag was added to gene: ISCA2.
Intellectual disability v2.893 GEMIN4 Ivone Leong Tag founder-effect tag was added to gene: GEMIN4.
Early onset or syndromic epilepsy v1.73 ASAH1 Rebecca Foulger Mode of inheritance for gene: ASAH1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.72 ASAH1 Rebecca Foulger Phenotypes for gene: ASAH1 were changed from to Spinal muscular atrophy with progressive myoclonic epilepsy, 159950
Intellectual disability v2.893 ITPA Ivone Leong Classified gene: ITPA as Green List (high evidence)
Intellectual disability v2.893 ITPA Ivone Leong Added comment: Comment on list classification: Promoted from red to green. ITPA is associated with a phenotype in OMIM but not in Gene2Phenotype. There are 5 unrelated families (PMID: 26224535, 30816001) with affected individuals who have global developmental delay with different variants in ITPA. PMID: 19498443 describes a knockout mouse model of Itpa, which had growth retardation. Therefore, there is enough evidence to promote this gene to green status.
Intellectual disability v2.893 ITPA Ivone Leong Gene: itpa has been classified as Green List (High Evidence).
Intellectual disability v2.892 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535; 30816001
Intellectual disability v2.891 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535; 30816001
Intellectual disability v2.891 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535; 30816001
Intellectual disability v2.891 ITPA Ivone Leong Publications for gene: ITPA were set to 26224535
Unexplained kidney failure in young people v1.71 GLA Eleanor Williams Classified gene: GLA as Green List (high evidence)
Unexplained kidney failure in young people v1.71 GLA Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team it was decided to rate this gene green on the 100K panel.
Unexplained kidney failure in young people v1.71 GLA Eleanor Williams Gene: gla has been classified as Green List (High Evidence).
Unexplained kidney failure in young people v1.70 GLA Eleanor Williams Phenotypes for gene: GLA were changed from to renal insufficiency; renal failure; Fabry disease, 301500
Unexplained kidney failure in young people v1.69 GLA Eleanor Williams Publications for gene: GLA were set to
Unexplained kidney failure in young people v1.68 GLA Eleanor Williams changed review comment from: This gene has been reviewed by Daniel Gale on the Unexplained paediatric onset end-stage renal disease panel 2019-05-08.; to: This gene has been reviewed by Daniel Gale on the Unexplained paediatric onset end-stage renal disease panel 2019-05-08. He states that "Fabry disease may present with renal limited disease, including presentation at end stage renal failure with no other clinical features (typically in young adults in their 20s). This has been repeatedly described in cohorts of people with kidney failure, ascertained either using biochemical or genetic screening."
Unexplained kidney failure in young people v1.68 GLA Eleanor Williams commented on gene: GLA: GLA is associated with Fabry disease (#301500) in OMIM

PMID: 28006774 - Turkmen et al 2016 - 3 out of 313 chronic kidney disease patients not receiving renal replacement therapy (0.95%) were diagnosed of Fabry disease by GLA gene mutation analysis. The age of the patients and their family members with Fabry disease ( total number =11) was 41.3 +/- 14.5.

PMID: 15861341 - Cybulla et al 2005 - describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. The index patient was 35 years old. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet).

PMID: 15100373 - Kotanko et al 2004 - Nationwide screening of Anderson-Fabry disease among dialysis patients in Austria. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene, Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. Age at start of dialysis ranged from 27 to 53.
Unexplained kidney failure in young people v1.68 GLA Eleanor Williams commented on gene: GLA
Rare multisystem ciliopathy disorders v1.115 POC1B Eleanor Williams changed review comment from: Amber rating confirmed with the Genomics England rare disease clinical team.; to: Amber rating confirmed with the Genomics England rare disease clinical team. This appears to be a single organ presentation of a disorder affecting cilia. It is appropriately green on the retinal disorders panel.
Rare multisystem ciliopathy disorders v1.115 POC1B Eleanor Williams commented on gene: POC1B: Amber rating confirmed with the Genomics England rare disease clinical team.
Hereditary haemorrhagic telangiectasia v1.49 EPHB4 Louise Daugherty Classified gene: EPHB4 as Green List (high evidence)
Hereditary haemorrhagic telangiectasia v1.49 EPHB4 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.
Hereditary haemorrhagic telangiectasia v1.49 EPHB4 Louise Daugherty Gene: ephb4 has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.115 LBR Eleanor Williams commented on gene: LBR: The Genomics England rare disease clinical team feedback is that the phenotype described to date (apart from polydactyly) does not strongly suggest a multi-system ciliopathy. If new evidence emerges of multi-system involvement in the ciliopathy spectrum then the rating can be reviewed.
Hereditary haemorrhagic telangiectasia v1.48 EPHB4 Louise Daugherty Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2; 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM
Hereditary haemorrhagic telangiectasia v1.47 EPHB4 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Hereditary haemorrhagic telangiectasia panel
Hereditary haemorrhagic telangiectasia v1.47 EPHB4 Louise Daugherty Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196 to Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM
Hereditary haemorrhagic telangiectasia v1.46 EPHB4 Louise Daugherty Added comment: Comment on publications: Added PMID: 30760892 from external reviewer to support upgrading of gene to Green
Hereditary haemorrhagic telangiectasia v1.46 EPHB4 Louise Daugherty Publications for gene: EPHB4 were set to 28687708; 28730721
Hereditary haemorrhagic telangiectasia v1.45 EPHB4 Louise Daugherty Mode of inheritance for gene: EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cystic kidney disease v1.48 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Cystic kidney disease v1.47 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 20558538; 22034641
Unexplained kidney failure in young people v1.68 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Unexplained kidney failure in young people v1.67 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 20558538; 22034641
Unexplained kidney failure in young people v1.66 PKD1 Eleanor Williams Added comment: Comment on mode of inheritance: Updating the Mode of Inheritance to include the biallelic cases (PMIDs: * 20558538, 23624871)
Unexplained kidney failure in young people v1.66 PKD1 Eleanor Williams Mode of inheritance for gene: PKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v0.19 PKD1 Eleanor Williams Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Unexplained young onset end-stage renal disease v0.18 PKD1 Eleanor Williams Publications for gene: PKD1 were set to 19165178; 22034641; 20558538
Fetal anomalies v0.287 PKD1 Eleanor Williams Added comment: Comment on mode of inheritance: updating MOI as biallelic cases have a more severe form of the disease
Fetal anomalies v0.287 PKD1 Eleanor Williams Mode of inheritance for gene: PKD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.115 DCDC2 Rebecca Foulger Classified gene: DCDC2 as Red List (low evidence)
Rare multisystem ciliopathy disorders v1.115 DCDC2 Rebecca Foulger Added comment: Comment on list classification: Downgraded rating from Amber to Red following advice from Genomics England clinical team: Not a multi-system ciliopathy and therefore Red rating is appropriate. Note that DCDC2 is Green on the
Neonatal cholestasis panel, which is the appropriate panel for this gene.
Rare multisystem ciliopathy disorders v1.115 DCDC2 Rebecca Foulger Gene: dcdc2 has been classified as Red List (Low Evidence).
Rare multisystem ciliopathy disorders v1.114 IFT81 Rebecca Foulger commented on gene: IFT81: Amber rating agreed with Genomics England Clinical team: Gene is in the right pathway but 3/4 cases to date have one variant that is not able to be classified as pathogenic/likely pathogenic.
Lipodystrophy - childhood onset v1.3 CAV1 Kevin Colclough edited their review of gene: CAV1: Added comment: 5 different loss of function variants have been reported in CAV1 to date associated with a lipodystrophy phenotype. No missense variants reported. GnomAD pLi score of 0.67 does not suggest that CAV1 is intolerant to loss of function variants.

Both heterozygous and homozygous LoF variants have been reported in patients with congenital lipodystrophy (PMID: 18211975, 25898808, 18237401).

A heterozygous c.-88del variant within the 5'UTR was identified in a patient with adult-onset partial lipodystrophy but with no proposed mechanism for a pathogenic effect on CAV1 (PMID: 18237401; the authors incorrectly described this a frameshift variant).

Frameshift variants within the C-terminal region of the gene that are predicted to escape NMD have been reported in patients with PAH but no lipodystrophy phenotype (PMID: 22474227).; Changed publications: PMID: 18390817, 18237401, 18211975, 25898808, 26176221, 22474227, 27717241, 11739396, 23049990; Changed phenotypes: ?Lipodystrophy, congenital generalized, type 3, 612526, Lipodystrophy, familial partial, type 7, 606721
Lipodystrophy - childhood onset v1.3 CAV1 Kevin Colclough gene: CAV1 was added
gene: CAV1 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: CAV1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CAV1 were set to PMID: 18390817; 18237401; 18211975; 25898808; 26176221; 27717241; 11739396; 23049990
Phenotypes for gene: CAV1 were set to ?Lipodystrophy, congenital generalized, type 3, 612526
Penetrance for gene: CAV1 were set to Complete
Review for gene: CAV1 was set to AMBER
gene: CAV1 was marked as current diagnostic
Added comment: Sources: Expert Review
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomics Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomic Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Control populations:
A search for the smallest CNV in a patient with craniosynostosis from Molin et al 2015 in the Database of Genomics Variants using GRCh38 coordinates shows no invidiuals from control populations with CNVs that cover RUNX2 http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg38/?name=chr6%3A45265488-45551053;search=Search.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals and CNVs covering RUNX2 were not found in the Database of Genomics Variants. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Intellectual disability v2.890 ITPA Ivone Leong Phenotypes for gene: ITPA were changed from Epileptic encephalopathy, early infantile, 35 to Epileptic encephalopathy, early infantile, 35, 616647
Intellectual disability v2.889 ISCA2 Ivone Leong Publications for gene: ISCA2 were set to 25539947; 29297947; 29359243; 29122497; 28356563
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Intellectual disability v2.888 ISCA2 Ivone Leong Publications for gene: ISCA2 were set to 25539947, 29297947, 29359243
Intellectual disability v2.887 GEMIN4 Ivone Leong commented on gene: GEMIN4
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis. ; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary:

Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams changed review comment from: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. No segregation analysis given.

PMID: McGee-Lawrence et al 2013 - Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. To determine whether Runx2 contributes to the etiology of Axin2 deficiency-induced craniosynostosis, they generated Axin2(-/-):Runx2(+/-) mice. These double mutant mice had longer skulls than Axin2(-/-) mice, indicating that Runx2 haploinsufficiency rescued the craniosynostosis phenotype of Axin2(-/-) mice

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic Patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Frequency of CNVs covering this region in the general population have not been reported.; to: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They state that this CNV was not found in 2,493 control individuals [Itsara et al., 2009]. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. They note that his multisutural craniosynostosis is the most extensive associated with RUNX2. No segregation analysis given.

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Mouse models:

PMIDs: 11581292 (Liu et al 2001) and 12167715 (Geoffroy et al 2002) - both surprisingly report transgenic mice overexpressing Cbfa1 (runx2) developed severe osteopenia.

PMID: 21807129 - Maeno et al 2011 - report that in mice early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis.

PMID: 23300083 McGee-Lawrence et al 2013 - Runx2-deficient mice die at birth because of a lack of skeletal ossification. Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. They state that their data are consistent with the idea that Runx2 plays a central role in the etiologies of several different forms of craniosynostosis.

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Mefford et al state the CNV they report was not found in 2,493 control individuals. Mouse models give conflicting evidence. Mouse models of runx2 over-expression surprisingly found they developed severe osteopenia. However, early onset of Runx2 expression resulted in craniosynostosis, and Runx2 was found to repress Axin2, low levels of which can result in craniosynostosis.
Intellectual disability v2.887 ISCA2 Ivone Leong Phenotypes for gene: ISCA2 were changed from Multiple mitochondrial dysfunctions syndrome 4 to Multiple mitochondrial dysfunctions syndrome 4, 616370
Intellectual disability v2.886 GEMIN4 Ivone Leong Phenotypes for gene: GEMIN4 were changed from Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, 617913
Rare syndromic craniosynostosis or isolated multisuture synostosis v1.123 RUNX2 Eleanor Williams commented on gene: RUNX2: Loss of functional mutations associated with CLEIDOCRANIAL DYSPLASIA in Gene2Phenotype (confirmed).
In OMIM loss of function mutations are associated with several phenotypes including Cleidocranial dysplasia.
A heterozygous duplication of some exons of RUNX2 is associated with Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly . However, craniosynostosis is not listed as a feature of this disorder (PMID:  23290074, 25311905, 29891876

CNV EVIDENCE:

PMID: 20683987 - Mefford et al 2010 - Evaluated 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications using whole-genome array CGH. They identified a heterozygous inverted 1.1 Mb duplication including the entire sequence of RUNX2, MIR586, and some of CLIC5 and SUPT3H in two affected cousins (1007 and 1019) with metopic synostosis and hypodontia. The duplication was inherited from the mother of one individual and it is presumed the father of the second individual (DNA not available, mother does not have the duplication). Both carrier parents have hypodontia by report, but neither is known to have had synostosis suggesting incomplete penetrance for that phenotype. The grandfather of 1007 and 1019 is described as having an abnormal head shape with a narrow forehead and several missing teeth; DNA was not available from this individual. They compared RUNX2 expression levels in osteoblasts from these two individuals to expression levels in osteoblasts from unaffected individuals (n = 6) and individuals with synostosis but without duplication of RUNX2 (n = 22). The average expression of RUNX2 in the samples from the two individuals was higher than all affected and unaffected cell lines but it was not a statistically significant difference in RUNX2 expression levels so should be interpreted with caution.

PMID: 23307468 - Varvagiannis et al 2013 - a girl with a de novo trisomy 6p12.3-p21.1 who showed craniosynostosis, manifested by the premature fusion of the right coronal and sagittal sutures, and also facial anomalies, psychomotor delay, and recurrent respiratory tract infections. MLPA analysis suggested a duplication of the entire RUNX2 gene. MLPA analysis indicated that the duplication was not present in parental blood samples. SNP array analysis identified the duplication was 6.9 Mb in size and mapped to 6p12.3–p21.1 (chr6: 40,797,975–47,701,961 NCBI Build 35; May 2004), thus encompassing 163 ENSEMBL genes. The finding of abnormal fontanelles and/or abnormal sutures, either manifested as craniosynostosis or not, has been documented in 5 cases in patients with pure partial trisomy 6p. No analysis of RUNX2 expression was performed.

PMID: 23348268 - Greives et al 2013 - present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. He presented as an infant with airway obstruction from choanal atresia. He was diagnosed with a closed anterior fontanelle, ventricular septal defect, restricted range of motion in his elbows, mild conductive hearing loss, and developmental delays. No segregation analysis given.

PMID: McGee-Lawrence et al 2013 - Axin2-deficient mice develop craniosynostosis because of high β-catenin activity. Runx2 represses transcription of Axin2 mRNA. To determine whether Runx2 contributes to the etiology of Axin2 deficiency-induced craniosynostosis, they generated Axin2(-/-):Runx2(+/-) mice. These double mutant mice had longer skulls than Axin2(-/-) mice, indicating that Runx2 haploinsufficiency rescued the craniosynostosis phenotype of Axin2(-/-) mice

PMID:25899668 - Molin et al 2015 - report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. The mother and one child had isolated hypodontia without craniosynostosis. The clinical presentation shown by syndromic Patients IV‐1 and IV‐3 appears radically different from MDMHB, but shares a few similarities with previously duplication patients, including as hypodontia and craniosynostosis. Isolated hypodontia observed in Patients III‐2 and IV‐2 highlights a wider clinical spectrum associated with RUNX2 duplication, in addition to isolated and syndromic craniosynostosis and MDMHB.

Decipher - there are 6 patients with RUNX2 duplications over 1 kb in size. None mention craniosynostosis as a feature, although abnormality of the face/triangular face is listed for the patient with the 3.59 Mb duplication. https://decipher.sanger.ac.uk/gene/RUNX2#variants/RUNX2/patient-overlap/cnvs

Summary: Loss of function variants, partial duplication of the the RUNX2 gene and full duplication of the RUNX2 gene appear to result in different phenotypes. With regards to full duplication, there are 4 cases reported in separate publications of duplications fully covering the RUNX2 gene and patients with a craniosynostosis phenotype. The smallest duplication is 285 kb and includes RUNX2 and the 5' half of SUPT3H. However, there appears to be incomplete penetrance with some carriers having a less severe phenotype. Frequency of CNVs covering this region in the general population have not been reported.
Intellectual disability v2.885 CWC27 Ivone Leong Phenotypes for gene: CWC27 were changed from Retinitis pigmentosa with or without skeletal anomalies to Retinitis pigmentosa with or without skeletal anomalies, 250410
Familial non syndromic congenital heart disease v1.46 ABL1 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Red based on advice from Helen Brittain. Wang et al. 2017 (PMID:28288113) report ABL1 germline variants (2 variants, 4 families) cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. ABL1 is on this heart panel based on ventral/atrial septal defects (VSD/ASD) seen in individuals from all four families in PMID:28288113.; to: Comment on list classification: Updated rating from Amber to Green based on advice from Helen Brittain. Wang et al. 2017 (PMID:28288113) report ABL1 germline variants (2 variants, 4 families) cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. ABL1 is on this heart panel based on ventral/atrial septal defects (VSD/ASD) seen in individuals from all four families in PMID:28288113.
Childhood solid tumours v1.25 WRN Ivone Leong Source Expert list was added to WRN.
Source Expert Review Green was added to WRN.
Mode of inheritance for gene WRN was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Werner syndrome, 277700 for gene: WRN
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 VHL Ivone Leong Source Expert list was added to VHL.
Source Expert Review Green was added to VHL.
Mode of inheritance for gene VHL was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes von Hippel-Lindau syndrome, 193300 for gene: VHL
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 SUFU Ivone Leong Source Expert list was added to SUFU.
Source Expert Review Green was added to SUFU.
Mode of inheritance for gene SUFU was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Medulloblastoma, desmoplastic, 155255; Basal cell nevus syndrome, 109400 for gene: SUFU
Publications for gene SUFU were changed from to 19533801; 29186568; 22829011; 25403219
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 STK11 Ivone Leong Source Expert list was added to STK11.
Source Expert Review Green was added to STK11.
Mode of inheritance for gene STK11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Peutz-Jeghers syndrome, 175200 for gene: STK11
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 SMAD4 Ivone Leong Source Expert list was added to SMAD4.
Source Expert Review Green was added to SMAD4.
Mode of inheritance for gene SMAD4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Polyposis, juvenile intestinal, 174900 for gene: SMAD4
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 PDGFRA Ivone Leong Source Expert list was added to PDGFRA.
Source Expert Review Green was added to PDGFRA.
Mode of inheritance for gene PDGFRA was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Familial Gastrointestinal stromal tumour; Gastrointestinal stromal tumor, somatic, 606764 for gene: PDGFRA
Publications for gene PDGFRA were changed from to 17566086; 14699510; 25975287; 17087943
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 MEN1 Ivone Leong Source Expert list was added to MEN1.
Source Expert Review Green was added to MEN1.
Mode of inheritance for gene MEN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Multiple endocrine neoplasia 1, 131100 for gene: MEN1
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.25 BMPR1A Ivone Leong Source Expert list was added to BMPR1A.
Source Expert Review Green was added to BMPR1A.
Mode of inheritance for gene BMPR1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Hereditary Mixed Polyposis Syndrome 2, 610069; Polyposis, juvenile intestinal, 174900 for gene: BMPR1A
Publications for gene BMPR1A were changed from to 23539595; 12136244; 11536076; 11381269
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v1.24 SUFU Ivone Leong reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 19533801, 22829011, 25403219, 29186568; Phenotypes: ; Mode of inheritance: None
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.; to: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.
Watch list tag has been removed as sufficient variants have now been reported.
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh Classified gene: TAB2 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.
Familial non syndromic congenital heart disease v1.46 TAB2 Sarah Leigh Gene: tab2 has been classified as Green List (High Evidence).
Familial non syndromic congenital heart disease v1.45 TAB2 Sarah Leigh Tag watchlist was removed from gene: TAB2.
Childhood solid tumours v1.24 PDGFRA Ivone Leong reviewed gene: PDGFRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17087943, 14699510, 25975287, 17566086; Phenotypes: ; Mode of inheritance: None
Childhood solid tumours v1.24 BMPR1A Ivone Leong reviewed gene: BMPR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381269, 12136244, 11536076; Phenotypes: ; Mode of inheritance: None
Intellectual disability v2.884 CUX2 Sarah Leigh Classified gene: CUX2 as Green List (high evidence)
Intellectual disability v2.884 CUX2 Sarah Leigh Added comment: Comment on list classification: Following personal comunication with Gemma Louise Carvill, the variant was confirmed as de novo in all nine cases mentioned in PMID 29630738.
Intellectual disability v2.884 CUX2 Sarah Leigh Gene: cux2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.212 XPO5 Eleanor Williams Phenotypes for gene: XPO5 were changed from to Nephrotic syndrome
Proteinuric renal disease v1.211 XPO5 Eleanor Williams Publications for gene: XPO5 were set to
Proteinuric renal disease v1.210 SLC19A3 Eleanor Williams Phenotypes for gene: SLC19A3 were changed from Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive; (originally on the Imerslund-Grasbeck syndrome gene panel) to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) #607483; (originally on the Imerslund-Grasbeck syndrome gene panel)
Proteinuric renal disease v1.209 NXF5 Eleanor Williams Phenotypes for gene: NXF5 were changed from to FSGS; heart-block disorder
Proteinuric renal disease v1.208 NXF5 Eleanor Williams Publications for gene: NXF5 were set to
Proteinuric renal disease v1.207 NLRP3 Eleanor Williams Phenotypes for gene: NLRP3 were changed from to SRNS
Proteinuric renal disease v1.206 NLRP3 Eleanor Williams Publications for gene: NLRP3 were set to
Proteinuric renal disease v1.205 NEU1 Eleanor Williams Phenotypes for gene: NEU1 were changed from to SRNS
Proteinuric renal disease v1.204 NEU1 Eleanor Williams Publications for gene: NEU1 were set to
Proteinuric renal disease v1.203 NEIL1 Eleanor Williams Phenotypes for gene: NEIL1 were changed from to SRNS
Proteinuric renal disease v1.202 NEIL1 Eleanor Williams Publications for gene: NEIL1 were set to
Proteinuric renal disease v1.201 LAMA5 Eleanor Williams Publications for gene: LAMA5 were set to
Proteinuric renal disease v1.200 KANK4 Eleanor Williams Publications for gene: KANK4 were set to
Proteinuric renal disease v1.199 KANK1 Eleanor Williams Phenotypes for gene: KANK1 were changed from to Steroid sensitive resistant nephrotic syndrome
Proteinuric renal disease v1.198 KANK1 Eleanor Williams Publications for gene: KANK1 were set to
Proteinuric renal disease v1.197 E2F3 Eleanor Williams Phenotypes for gene: E2F3 were changed from to FSGS; mental retardation
Proteinuric renal disease v1.196 E2F3 Eleanor Williams Publications for gene: E2F3 were set to
Proteinuric renal disease v1.195 CYP11B2 Eleanor Williams Phenotypes for gene: CYP11B2 were changed from to Hypoaldosteronism, congenital, due to CMO I deficiency #203400; Hypoaldosteronism, congenital, due to CMO II deficiency #610600
Proteinuric renal disease v1.194 CYP11B2 Eleanor Williams Publications for gene: CYP11B2 were set to
Proteinuric renal disease v1.193 COQ9 Eleanor Williams Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5 #614654
Proteinuric renal disease v1.192 COQ9 Eleanor Williams Publications for gene: COQ9 were set to
Proteinuric renal disease v1.191 COQ7 Eleanor Williams Phenotypes for gene: COQ7 were changed from to ?Coenzyme Q10 deficiency, primary, 8 #616733
Proteinuric renal disease v1.190 COQ7 Eleanor Williams Publications for gene: COQ7 were set to
Intellectual disability v2.883 CHKB Ivone Leong Classified gene: CHKB as Green List (high evidence)
Intellectual disability v2.883 CHKB Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on expert review. CHKB is associated with a phenotype in OMIM but not in Gene2Phenotype. There are >10 unrelated cases with different variants reported in the literature of patients with congenital muscular dystrophy who also have intellectual disability.
Intellectual disability v2.883 CHKB Ivone Leong Gene: chkb has been classified as Green List (High Evidence).
Intellectual disability v2.882 CHKB Ivone Leong Publications for gene: CHKB were set to 21665002
Mitochondrial disorders v1.400 MTPAP Sarah Leigh Publications for gene: MTPAP were set to 20970105; 25008111; 26319014
Mitochondrial disorders v1.399 IARS2 Sarah Leigh Classified gene: IARS2 as Amber List (moderate evidence)
Mitochondrial disorders v1.399 IARS2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 2 variants reported, together with supportive functional studies.
Mitochondrial disorders v1.399 IARS2 Sarah Leigh Gene: iars2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.398 IARS2 Sarah Leigh Added comment: Comment on phenotypes: ?Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia 616007, also known as CAGSSS
Mitochondrial disorders v1.398 IARS2 Sarah Leigh Phenotypes for gene: IARS2 were changed from No OMIM phenotype; CAGSSS - Cataracts (CA), growth hormone deficiency (G), sensory neuropathy (S), sensorineural hearing loss (S), and skeletal dysplasia (S) to ?Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia 616007
Possible mitochondrial disorder - nuclear genes v0.202 IARS2 Sarah Leigh Publications for gene: IARS2 were set to
Mitochondrial disorders v1.397 IARS2 Sarah Leigh changed review comment from: Comment on publications: PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene)
PMID: 27078007 (full text not available to confirm findings).; to: Comment on publications: PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene)
PMID: 27078007 reports the phenotypical classification of case of Infantile Cataract, Congenital Neurotrophic Keratitis, and Orbital Myopathy in one of the cases mentioned in PMID: 25130867.
.
Mitochondrial disorders v1.397 IARS2 Sarah Leigh Added comment: Comment on publications: PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene)
PMID: 27078007 (full text not available to confirm findings).
Mitochondrial disorders v1.397 IARS2 Sarah Leigh Publications for gene: IARS2 were set to PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene); PMID: 27078007 (full text not available to confirm findings).
Cytopenias and congenital anaemias v1.70 RUNX1 Louise Daugherty Tag somatic-germline was removed from gene: RUNX1.
Tag somatic tag was added to gene: RUNX1.
Cytopenias and congenital anaemias v1.70 PIGT Louise Daugherty Tag somatic-germline was removed from gene: PIGT.
Tag somatic tag was added to gene: PIGT.
Cytopenias and congenital anaemias v1.70 PIGT Louise Daugherty Publications for gene: PIGT were set to
Cytopenias and congenital anaemias v1.69 MPL Louise Daugherty Tag somatic-germline was removed from gene: MPL.
Tag somatic tag was added to gene: MPL.
Cytopenias and congenital anaemias v1.69 IKZF1 Louise Daugherty Tag somatic-germline was removed from gene: IKZF1.
Tag somatic tag was added to gene: IKZF1.
Cytopenias and congenital anaemias v1.69 GATA2 Louise Daugherty Tag somatic-germline was removed from gene: GATA2.
Tag somatic tag was added to gene: GATA2.
Cytopenias and congenital anaemias v1.69 CEBPA Louise Daugherty Tag somatic-germline was removed from gene: CEBPA.
Tag somatic tag was added to gene: CEBPA.
Early onset or syndromic epilepsy v1.71 RRM2B Rebecca Foulger Classified gene: RRM2B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v1.71 RRM2B Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber after reviewing the literature evidence. The main phenotype manifests as hypotonia with lactic acidosis. Although seizures have been reported, they are variable and not common (PMID:29241262 summary records seizures in 6/78 patients, PMID:18504129 don't report seizures in any of their three patients).
Early onset or syndromic epilepsy v1.71 RRM2B Rebecca Foulger Gene: rrm2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v1.70 RRM2B Rebecca Foulger Publications for gene: RRM2B were set to
Early onset or syndromic epilepsy v1.69 RRM2B Rebecca Foulger Phenotypes for gene: RRM2B were changed from Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; seizures to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; seizures; status epilepticus
Early onset or syndromic epilepsy v1.68 RRM2B Rebecca Foulger commented on gene: RRM2B: Bourdon et al., 2007 (PMID:17486094) studied 7 cases of mitochondrial depletion in 4 unrelated families with RRM2B variants. Seizures were reported in Family 2: Subject 4 showed trunk hypotonia and tubulopathy shortly after birth. At 20 days of life he developed seizures, and died at 2 months after status epilepticus. His sister (Subject 5) had a similar clinical course (the authors don't explicitly state whether she had seizures).
Early onset or syndromic epilepsy v1.68 RRM2B Rebecca Foulger changed review comment from: PMID:19138848 report two Sudanese brothers with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene. Both brothers had seizures amongst their phenotypes.; to: PMID:19138848 (Kollberg et al., 2009) report two Sudanese brothers with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene. Both brothers had seizures amongst their phenotypes.
Early onset or syndromic epilepsy v1.68 RRM2B Rebecca Foulger Phenotypes for gene: RRM2B were changed from to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; seizures
Early onset or syndromic epilepsy v1.67 RRM2B Rebecca Foulger Mode of inheritance for gene: RRM2B was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.66 RRM2B Rebecca Foulger commented on gene: RRM2B: Bornstein et al., 2008 (PMID:18504129) sequenced the RRM2B gene in 3 unrelated cases- The common clinical feature was myopathy with lactic acidosis, and none had overt seizures.
Early onset or syndromic epilepsy v1.66 RRM2B Rebecca Foulger commented on gene: RRM2B: PMID:19138848 report two Sudanese brothers with a severe form of fatal autosomal recessive encephalomyopathic mtDNA depletion syndrome-8B caused by a homozygous mutation in the RRM2B gene. Both brothers had seizures amongst their phenotypes.
Early onset or syndromic epilepsy v1.66 CUX2 Rebecca Foulger Phenotypes for gene: CUX2 were changed from Seizures; Intellectual disability; Autistic behavior; Developmental epileptic encephalopathy to Seizures; Epileptic encephalopathy, early infantile, 67, 618141; Infantile onset myoclonic epileptic encephalopathy
Early onset or syndromic epilepsy v1.65 CUX2 Rebecca Foulger Classified gene: CUX2 as Green List (high evidence)
Early onset or syndromic epilepsy v1.65 CUX2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following discussion with Sarah Leigh. A personal communication from the authors of PMID:29630738 confirm that the variants seen in 9 patients were de novo and therefore not Founder effect. Although there is no functional data and there is limited information about the patients in PMIDs:29630738, 23020937 and 23934111, overall there are sufficient cases (10 individuals from 4 papers including 2 large-scale studies) and 2 Green reviews to support inclusion on the panel as a Green gene. Plus CUX2 is now associated with an EIEE disorder in OMIM.
Early onset or syndromic epilepsy v1.65 CUX2 Rebecca Foulger Gene: cux2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v1.64 CUX2 Rebecca Foulger commented on gene: CUX2: A summary of evidence: ONE variant (Glu590Lys) reported from 9 patients in Chatron et al., 2018 (PMID:29630738) and 1 patient in Barington et al., 2018 (PMID:29795476). Barington et al claim their Danish patient is a third case as there are additionally two large scale reports from Rauch et al., 2012 (PMID:23020937) and the Epi4K Consortium (Allen et al., 2013, PMID:23934111)- there is sparse information about the patients in the large-scale papers, although the Epi4K patient is a German male. Two of the 9 patients in Chatron et al came from these large-scale studies. None of the papers perform functional studies. CUX2 was previously rated Amber as there was a question mark over the relatedness of patients in Chatron et al (this has been addressed by a pers.comm from Gemma Carvill).
Early onset or syndromic epilepsy v1.64 CUX2 Rebecca Foulger commented on gene: CUX2: Re-assessing the rating of CUX2 following a new Green review by Deb Pals (the new review contains the same paper (PMID:29630738) as described by Konstantinos Varvagiannis). CUX2 is now associated with an OMIM disorder: Epileptic encephalopathy, early infantile, 67, 618141. The DD-Gene2Phenotype rating is still probable.
Early onset or syndromic epilepsy v1.64 CUX2 Rebecca Foulger commented on gene: CUX2
Early onset or syndromic epilepsy v1.64 RRM2B Rebecca Foulger commented on gene: RRM2B
Intellectual disability v2.881 BRD4 Ivone Leong Classified gene: BRD4 as Green List (high evidence)
Intellectual disability v2.881 BRD4 Ivone Leong Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team. Promoted from red to green based on the evidence provided by Konstantinos Varvagiannis (Other). BRD4 is not associated with a phenotype in OMIM and in Gene2Phenotype it is reported to be probably associated with Cornelia de Lange-like syndrome. Intellectual disability (medium to severe) is a phenotype of Cornelia de Lange-like syndrome.
Intellectual disability v2.881 BRD4 Ivone Leong Gene: brd4 has been classified as Green List (High Evidence).
Limb disorders v1.7 SOX9 Louise Daugherty Tag duplication was removed from gene: SOX9.
Tag gene-duplication tag was added to gene: SOX9.
Intellectual disability v2.880 SETD1B Ivone Leong Classified gene: SETD1B as Green List (high evidence)
Intellectual disability v2.880 SETD1B Ivone Leong Added comment: Comment on list classification: Promoted from amber to green as there is now sufficient evidence to support a gene-disease association, based on submitted reviews.
Intellectual disability v2.880 SETD1B Ivone Leong Gene: setd1b has been classified as Green List (High Evidence).
Intellectual disability v2.879 SETD1B Ivone Leong Publications for gene: SETD1B were set to 29322246; 27106595; 25428890
Intellectual disability v2.878 SETD1B Ivone Leong reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31110234; Phenotypes: ; Mode of inheritance: None
Hereditary haemorrhagic telangiectasia v1.44 EPHB4 Claire Shovlin reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28687708 PMID: 30760892; Phenotypes: capillary malformation, epistaxis, telangiectasia, cerebral AVM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Proteinuric renal disease v1.189 COL4A1 Eleanor Williams Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps #611773
Proteinuric renal disease v1.188 COL4A1 Eleanor Williams Publications for gene: COL4A1 were set to
Proteinuric renal disease v1.187 CDK20 Eleanor Williams Phenotypes for gene: CDK20 were changed from to Chronic kidney disease
Proteinuric renal disease v1.186 CDK20 Eleanor Williams Publications for gene: CDK20 were set to
Proteinuric renal disease v1.185 CD151 Eleanor Williams Phenotypes for gene: CD151 were changed from to Nephropathy with pretibial epidermolysis bullosa and deafness #609057
Proteinuric renal disease v1.184 CD151 Eleanor Williams Publications for gene: CD151 were set to
Proteinuric renal disease v1.183 ARHGAP24 Eleanor Williams Phenotypes for gene: ARHGAP24 were changed from to Focal segmental glomerulosclerosis
Proteinuric renal disease v1.182 ARHGAP24 Eleanor Williams Publications for gene: ARHGAP24 were set to
Proteinuric renal disease v1.181 ANKFY1 Eleanor Williams Publications for gene: ANKFY1 were set to
Proteinuric renal disease v1.180 ZMPSTE24 Eleanor Williams Phenotypes for gene: ZMPSTE24 were changed from to Mandibuloacral dysplasia with type B lipodystrophy #608612
Proteinuric renal disease v1.179 ZMPSTE24 Eleanor Williams Publications for gene: ZMPSTE24 were set to
Proteinuric renal disease v1.178 VPS33B Eleanor Williams Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 #208085
Proteinuric renal disease v1.177 VPS33B Eleanor Williams Publications for gene: VPS33B were set to
Proteinuric renal disease v1.176 VIPAS39 Eleanor Williams Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2 # 613404
Proteinuric renal disease v1.175 VIPAS39 Eleanor Williams Publications for gene: VIPAS39 were set to
Proteinuric renal disease v1.174 TTC21B Eleanor Williams Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12 # 613820
Proteinuric renal disease v1.173 TTC21B Eleanor Williams Publications for gene: TTC21B were set to
Proteinuric renal disease v1.172 TPRKB Eleanor Williams Phenotypes for gene: TPRKB were changed from to Galloway-Mowat syndrome 5 #617731
Proteinuric renal disease v1.171 TPRKB Eleanor Williams Publications for gene: TPRKB were set to
Proteinuric renal disease v1.170 SYNPO Eleanor Williams Phenotypes for gene: SYNPO were changed from to Focal segmental glomerulosclerosis; FSGS
Proteinuric renal disease v1.169 SYNPO Eleanor Williams Publications for gene: SYNPO were set to
Proteinuric renal disease v1.168 PTPRO Eleanor Williams Phenotypes for gene: PTPRO were changed from to Nephrotic syndrome, type 6 #614196
Proteinuric renal disease v1.167 PTPRO Eleanor Williams Publications for gene: PTPRO were set to
Proteinuric renal disease v1.166 PMM2 Eleanor Williams Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia #212065
Proteinuric renal disease v1.165 PMM2 Eleanor Williams Publications for gene: PMM2 were set to
Proteinuric renal disease v1.164 NUP205 Eleanor Williams Phenotypes for gene: NUP205 were changed from to ?Nephrotic syndrome, type 13 #616893
Proteinuric renal disease v1.163 NUP205 Eleanor Williams Publications for gene: NUP205 were set to
Proteinuric renal disease v1.162 NUP160 Eleanor Williams Phenotypes for gene: NUP160 were changed from to ?Nephrotic syndrome, type 19 #618178
Proteinuric renal disease v1.161 NUP160 Eleanor Williams Publications for gene: NUP160 were set to
Proteinuric renal disease v1.160 NPHP4 Eleanor Williams Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4 #606966
Proteinuric renal disease v1.159 NPHP4 Eleanor Williams Publications for gene: NPHP4 were set to
Proteinuric renal disease v1.158 MEFV Eleanor Williams Phenotypes for gene: MEFV were changed from to Familial Mediterranean fever, AR #249100
Proteinuric renal disease v1.157 MAFB Eleanor Williams Phenotypes for gene: MAFB were changed from to FSGS with Duane retraction syndrome
Proteinuric renal disease v1.156 MAFB Eleanor Williams Publications for gene: MAFB were set to
Proteinuric renal disease v1.155 LMNA Eleanor Williams Phenotypes for gene: LMNA were changed from to Partial lipodystrophy and FSGS
Proteinuric renal disease v1.154 LMNA Eleanor Williams Publications for gene: LMNA were set to
Proteinuric renal disease v1.153 LCAT Eleanor Williams Phenotypes for gene: LCAT were changed from to Norum disease #245900
Proteinuric renal disease v1.152 KANK2 Eleanor Williams Phenotypes for gene: KANK2 were changed from Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome to Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome; Nephrotic syndrome 16 #617783
Proteinuric renal disease v1.151 KANK2 Eleanor Williams Publications for gene: KANK2 were set to J Clin Invest. 2015; 125(6):2375–2384
Proteinuric renal disease v1.150 ITSN2 Eleanor Williams Phenotypes for gene: ITSN2 were changed from to Early childhood SSNS
Proteinuric renal disease v1.149 ITSN2 Eleanor Williams Publications for gene: ITSN2 were set to
Proteinuric renal disease v1.148 ITGB4 Eleanor Williams Phenotypes for gene: ITGB4 were changed from to Epidermolysis bullosa, junctional, with pyloric stenosis #226730
Proteinuric renal disease v1.147 ITGB4 Eleanor Williams Publications for gene: ITGB4 were set to
Proteinuric renal disease v1.146 ITGA3 Eleanor Williams Phenotypes for gene: ITGA3 were changed from to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital #614748
Proteinuric renal disease v1.145 GAPVD1 Eleanor Williams Publications for gene: GAPVD1 were set to
Proteinuric renal disease v1.144 DGKE Eleanor Williams Phenotypes for gene: DGKE were changed from to Nephrotic syndrome, type 7 #615008
Proteinuric renal disease v1.143 DGKE Eleanor Williams Publications for gene: DGKE were set to
Proteinuric renal disease v1.142 CD2AP Eleanor Williams Phenotypes for gene: CD2AP were changed from to Glomerulosclerosis, focal segmental, 3 #607832
Proteinuric renal disease v1.141 CD2AP Eleanor Williams Publications for gene: CD2AP were set to
Proteinuric renal disease v1.140 ARHGDIA Eleanor Williams Phenotypes for gene: ARHGDIA were changed from to Nephrotic syndrome, type 8 #615224
Proteinuric renal disease v1.139 ARHGDIA Eleanor Williams Publications for gene: ARHGDIA were set to
Hereditary neuropathy v1.331 AP1S1 Alexander Rossor edited their review of gene: AP1S1: Added comment: Same homozygous mutation described in 4 families form same geographical region; Changed rating: AMBER
Hereditary neuropathy v1.331 XRCC1 Alexander Rossor edited their review of gene: XRCC1: Added comment: Only two families; Changed rating: AMBER; Changed publications: 29472272, 28002403
Hereditary neuropathy v1.331 SCYL1 Alexander Rossor edited their review of gene: SCYL1: Added comment: Neuropthay only in 2 unrelated patients; Changed rating: AMBER; Changed publications: 26581903, 30258122
Hereditary neuropathy v1.331 DNAJB2 Alexander Rossor edited their review of gene: DNAJB2: Added comment: Multiple families now reported with recessive CMT/ HMN. PMIDs added above; Changed publications: 26752306, 25274842, 22522442
Structural eye disease v0.83 SCLT1 Ivone Leong Publications for gene: SCLT1 were set to 29450879; 24285566; 27894351; 28486600; 30425282; 30237576; 24285566; 29450879
Structural eye disease v0.82 SCLT1 Ivone Leong Publications for gene: SCLT1 were set to 29450879; 24285566; 27894351; 28486600
Structural eye disease v0.81 KIAA0586 Ivone Leong reviewed gene: KIAA0586: Rating: AMBER; Mode of pathogenicity: ; Publications: 30055837; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.81 SCLT1 Anna de Burca reviewed gene: SCLT1: Rating: AMBER; Mode of pathogenicity: ; Publications: 30425282, 30237576, 24285566, 29450879; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.80 KIAA0586 Ivone Leong gene: KIAA0586 was added
gene: KIAA0586 was added to Structural eye disease. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: KIAA0586 was set to
Publications for gene: KIAA0586 were set to 30055837
Structural eye disease v0.80 SCLT1 Ivone Leong Source Expert Review Amber was added to SCLT1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Structural eye disease v0.79 TMEM237 Ivone Leong Classified gene: TMEM237 as Green List (high evidence)
Structural eye disease v0.79 TMEM237 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on expert review.
Structural eye disease v0.79 TMEM237 Ivone Leong Gene: tmem237 has been classified as Green List (High Evidence).
Structural eye disease v0.78 TMEM216 Ivone Leong Classified gene: TMEM216 as Green List (high evidence)
Structural eye disease v0.78 TMEM216 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on expert review.
Structural eye disease v0.78 TMEM216 Ivone Leong Gene: tmem216 has been classified as Green List (High Evidence).
Hereditary haemorrhagic telangiectasia v1.44 EPHB4 Ellen Thomas Classified gene: EPHB4 as Amber List (moderate evidence)
Hereditary haemorrhagic telangiectasia v1.44 EPHB4 Ellen Thomas Gene: ephb4 has been classified as Amber List (Moderate Evidence).
Hereditary haemorrhagic telangiectasia v1.43 EPHB4 Ellen Thomas gene: EPHB4 was added
gene: EPHB4 was added to Hereditary haemorrhagic telangiectasia. Sources: Other
Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHB4 were set to 28687708; 28730721
Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2; 618196
Penetrance for gene: EPHB4 were set to Incomplete
Review for gene: EPHB4 was set to AMBER
Added comment: At least one family in 100k recruited under HHT has a mutation in this gene as it's an overlap condition. Consider whether to include with the GLH specialist group for GMS diagnostic analysis.
Sources: Other
Hereditary neuropathy v1.331 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Rare multisystem ciliopathy disorders v1.114 POC1B Eleanor Williams Phenotypes for gene: POC1B were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Joubert Syndrome; Senior-Loken Syndrome 24 gene panel; Cone-rod dystrophy 20 615973; AUTOSOMAL-RECESSIVE CONE-ROD DYSTROPHY
Rare multisystem ciliopathy disorders v1.113 POC1B Eleanor Williams Publications for gene: POC1B were set to
Rare multisystem ciliopathy disorders v1.112 POC1B Eleanor Williams Classified gene: POC1B as Amber List (moderate evidence)
Rare multisystem ciliopathy disorders v1.112 POC1B Eleanor Williams Added comment: Comment on list classification: Multiple cases of a single feature (retinal dystrophy) disease, only one case plus disease model for multisystem ciliopathy. Rating Amber.
Rare multisystem ciliopathy disorders v1.112 POC1B Eleanor Williams Gene: poc1b has been classified as Amber List (Moderate Evidence).
Rare multisystem ciliopathy disorders v1.111 POC1B Eleanor Williams commented on gene: POC1B
Rare multisystem ciliopathy disorders v1.111 ALMS1 Rebecca Foulger changed review comment from: Addressed Red review from Beth Hoskins, imported from Bardet-Biedl Syndrome panel. ALMS1 is appropriate for this panel: Confirmed DDG2P gene for ALSTROM SYNDROME (a Ciliopathy) and sufficient cases from the literature/OMIM to support inclusion.; to: Addressing Red review from Beth Hoskins, imported from Bardet-Biedl Syndrome panel: ALMS1 is appropriate for this panel: Confirmed DDG2P gene for ALSTROM SYNDROME (a Ciliopathy) and sufficient cases from the literature/OMIM to support inclusion.
Rare multisystem ciliopathy disorders v1.111 ALMS1 Rebecca Foulger commented on gene: ALMS1
Rare multisystem ciliopathy disorders v1.111 TMEM67 Rebecca Foulger commented on gene: TMEM67
Rare multisystem ciliopathy disorders v1.111 PKD1 Rebecca Foulger Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I, 173900 to Polycystic kidney disease, adult type I, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)
Rare multisystem ciliopathy disorders v1.110 PKD1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from Monoallelic to both Monoallelic and Biallelic, based on review by Julia Baptista.
Rare multisystem ciliopathy disorders v1.110 PKD1 Rebecca Foulger Mode of inheritance for gene: PKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.109 PKD1 Rebecca Foulger Publications for gene: PKD1 were set to
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy. Plus functional information with IFT43 involved in ciliary transport.; to: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy. Plus functional role with IFT43 involved in ciliary transport.
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy.; to: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy. Plus functional information with IFT43 involved in ciliary transport.
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Short-rib thoracic dysplasia 18 with polydactyly, 617866; Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome to Short-rib thoracic dysplasia 18 with polydactyly, 617866; Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.108 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Short-rib thoracic dysplasia 18 with polydactyly, 617866; Sensenbrenner syndrome to Short-rib thoracic dysplasia 18 with polydactyly, 617866; Cranioectodermal dysplasia 3, 614099; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.107 IFT43 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel.; to: Comment on list classification: Updated rating from Amber to Green based on two Green reviews from Penny Clouston and Zornitza Stark. Sufficient cases in the literature to support inclusion on the Ciliopathy panel, including two cases of short-rib thoracic dysplasia with polydactyly from PMID:28400947. Plus confirmed rating in DDG2P for CRANIOECTODERMAL DYSPLASIA TYPE 3; CED3 (also known as Sensenbrenner syndrome) is a rare autosomal recessive heterogeneous ciliopathy.
Rare multisystem ciliopathy disorders v1.107 IFT43 Rebecca Foulger Phenotypes for gene: IFT43 were changed from Cranioectodermal dysplasia 3, 614099; Short-rib polydactyly syndrome; Sensenbrenner syndrome to Short-rib thoracic dysplasia 18 with polydactyly, 617866; Sensenbrenner syndrome
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger commented on gene: IFT81: Added watchlist tag.
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Tag watchlist tag was added to gene: IFT81.
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Classified gene: IFT81 as Amber List (moderate evidence)
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. Associated with OMIM:617895 but not yet associated with a disorder in Gene2Phenotype. Functional data supports a ciliopathy association: IFT81 is part of the IFT-B complex involved in the bidirectional transport of ciliary proteins. Green review from Zornitza based on 3 (or 4) individuals identified in the literature with a Cliopathy phenotype and biallelic IFT81 variants. However in the two cases from PMID:26275418, OMIM classes the variants as VUS. Therefore on balance have classed as Amber awaiting further cases or clarification of the variants in PMID:26275418.
Rare multisystem ciliopathy disorders v1.106 IFT81 Rebecca Foulger Gene: ift81 has been classified as Amber List (Moderate Evidence).
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger commented on gene: IFT81: Duran et al. 2016 (PMID:27666822) identify two individuals with skeletal ciliopathies: R98-443 with sphyxiating thoracic dystrophy (ATD), and R13-147A with Short-rib polydactyly syndromes (SRPS). Exome sequencing revealed compound het variants in IFT81 in both cases: p.Leu29Phe and p.Arg512* in R98-443, and p.Leu262* and p.Leu435del in R13-147A.
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger changed review comment from: Perrault et al., 2015 (PMID:26275418) screened 1628 individuals with reno-ocular ciliopathies by sequencing of ciliary candidate genes and identified recessive ITF81 variants in two consanguineous families with a ciliopathy phenotype.
They identified a homozygous variant in IFT81 in one individual (A3286-21) with a nephronophthisis-related ciliopathy, polydactyly and moderate intellectual disability (delayed speech and an IQ of 70). They identified a loss-of-stop variant in IFT81 in a second individual (NCK-033) with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy (RD), brain lesions and mild intellectual disability. The patient also harboured 9 additional rare homozygous variants including a missense change (Gly245Arg) in the gene PPT1, accounting for the clinical diagnosis of neuronal ceroid lipofuscinosis-1. Both these variants have currently been classed as VUS in OMIM.; to: Perrault et al., 2015 (PMID:26275418) screened 1628 individuals with reno-ocular ciliopathies by sequencing of ciliary candidate genes and identified recessive ITF81 variants in two consanguineous families with a ciliopathy phenotype.
They identified a homozygous variant in IFT81 in one individual (A3286-21) with a nephronophthisis-related ciliopathy, polydactyly and moderate intellectual disability (delayed speech and an IQ of 70). They identified a loss-of-stop variant in IFT81 in a second individual (NCK-033) with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy (RD), brain lesions and mild intellectual disability. The patient also harboured 9 additional rare homozygous variants including a missense change (Gly245Arg) in the gene PPT1, accounting for the clinical diagnosis of neuronal ceroid lipofuscinosis-1. Both these variants have currently been classed as VUS in OMIM.
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger commented on gene: IFT81
Rare multisystem ciliopathy disorders v1.105 IFT81 Rebecca Foulger Mode of inheritance for gene: IFT81 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.104 IFT81 Rebecca Foulger Phenotypes for gene: IFT81 were changed from to Short-rib thoracic dysplasia 19 with or without polydactyly, 617895
Rare multisystem ciliopathy disorders v1.103 IFT81 Rebecca Foulger Publications for gene: IFT81 were set to
Hereditary neuropathy v1.330 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.329 NOP56_GGCCTGTT Louise Daugherty Classified STR: NOP56_GGCCTGTT as No list
Hereditary neuropathy v1.329 NOP56_GGCCTGTT Louise Daugherty Added comment: Comment on list classification: this is a test -
Hereditary neuropathy v1.329 NOP56_GGCCTGTT Louise Daugherty Str: nop56_ggcctgtt has been removed from the panel.
Hereditary neuropathy v1.328 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.327 NOP56_GGCCTGTT Louise Daugherty Classified STR: NOP56_GGCCTGTT as Red List (low evidence)
Hereditary neuropathy v1.327 NOP56_GGCCTGTT Louise Daugherty Str: nop56_ggcctgtt has been classified as Red List (Low Evidence).
Hereditary neuropathy v1.326 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.325 NOP56_GGCCTGTT Louise Daugherty Classified STR: NOP56_GGCCTGTT as No list
Hereditary neuropathy v1.325 NOP56_GGCCTGTT Louise Daugherty Str: nop56_ggcctgtt has been removed from the panel.
Hereditary neuropathy v1.324 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Hereditary neuropathy v1.322 Louise Daugherty removed STR:NOP56_GGCCTGTT from the panel
Intellectual disability v2.878 COL4A3BP Louise Daugherty commented on gene: COL4A3BP
DDG2P v1.68 COL4A3BP Louise Daugherty commented on gene: COL4A3BP
Fetal anomalies v0.285 COL4A3BP Louise Daugherty commented on gene: COL4A3BP
Fetal anomalies v0.285 COL4A3BP Louise Daugherty Tag new-gene-name tag was added to gene: COL4A3BP.
DDG2P v1.68 COL4A3BP Louise Daugherty Tag new-gene-name tag was added to gene: COL4A3BP.
Intellectual disability v2.878 COL4A3BP Louise Daugherty Tag new-gene-name tag was added to gene: COL4A3BP.
Proteinuric renal disease v1.137 APOL1 Eleanor Williams Phenotypes for gene: APOL1 were changed from to Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551
Proteinuric renal disease v1.136 APOL1 Eleanor Williams Publications for gene: APOL1 were set to
Proteinuric renal disease v1.135 ANLN Eleanor Williams Publications for gene: ANLN were set to 24676636
Proteinuric renal disease v1.134 AMN Eleanor Williams Publications for gene: AMN were set to 12590260
Proteinuric renal disease v1.133 ALMS1 Eleanor Williams Phenotypes for gene: ALMS1 were changed from to Alstrom Syndrome #203800
Proteinuric renal disease v1.132 ALMS1 Eleanor Williams Publications for gene: ALMS1 were set to
Proteinuric renal disease v1.131 ALG1 Eleanor Williams Phenotypes for gene: ALG1 were changed from to Congenital disorder of glycosylation, type Ik #608540
Proteinuric renal disease v1.130 ALG1 Eleanor Williams Publications for gene: ALG1 were set to
Proteinuric renal disease v1.129 WT1 Eleanor Williams Phenotypes for gene: WT1 were changed from to Denys-Drash syndrome #194080; Frasier syndrome #136680; Wilms tumor, type 1 #194070
Proteinuric renal disease v1.128 WT1 Eleanor Williams Publications for gene: WT1 were set to
Proteinuric renal disease v1.127 WDR73 Eleanor Williams Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1 #251300
Proteinuric renal disease v1.126 WDR73 Eleanor Williams Publications for gene: WDR73 were set to
Proteinuric renal disease v1.125 TRPC6 Eleanor Williams Phenotypes for gene: TRPC6 were changed from to Glomerulosclerosis, focal segmental, 2 #603652; Proteinuria; FSGS; kidney failure; Familial and sporadic SRNS (adult)
Proteinuric renal disease v1.124 TRPC6 Eleanor Williams Publications for gene: TRPC6 were set to
Proteinuric renal disease v1.123 SMARCAL1 Eleanor Williams Phenotypes for gene: SMARCAL1 were changed from to Schimke immunoosseous dysplasia #242900
Proteinuric renal disease v1.122 SMARCAL1 Eleanor Williams Publications for gene: SMARCAL1 were set to
Proteinuric renal disease v1.121 SCARB2 Eleanor Williams Phenotypes for gene: SCARB2 were changed from to Action myoclonus renal failure syndrome; Epilepsy, progressive myoclonic 4, with or without renal failure #254900
Proteinuric renal disease v1.120 SCARB2 Eleanor Williams Publications for gene: SCARB2 were set to
Proteinuric renal disease v1.119 PLCE1 Eleanor Williams Phenotypes for gene: PLCE1 were changed from to Nephrotic syndrome, type 3 #610725; Congenital nephrotic syndrome/SRNS
Proteinuric renal disease v1.118 PLCE1 Eleanor Williams Publications for gene: PLCE1 were set to
Proteinuric renal disease v1.117 PDSS2 Eleanor Williams Phenotypes for gene: PDSS2 were changed from to Coenzyme Q10 deficiency, primary, 3 #614652; Leigh syndrome
Proteinuric renal disease v1.116 PDSS2 Eleanor Williams Publications for gene: PDSS2 were set to
Proteinuric renal disease v1.115 NUP93 Eleanor Williams Phenotypes for gene: NUP93 were changed from Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome to Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome; Nephrotic syndrome, type 12 #616892
Proteinuric renal disease v1.114 NUP93 Eleanor Williams Publications for gene: NUP93 were set to Am J Hum Genet. 2015 Oct 1; 97(4):555-66
Proteinuric renal disease v1.113 NPHS2 Eleanor Williams Phenotypes for gene: NPHS2 were changed from to Nephrotic syndrome, type 2 #600995
Proteinuric renal disease v1.112 NPHS1 Eleanor Williams Phenotypes for gene: NPHS1 were changed from to Nephrotic syndrome, type 1 #602716
Proteinuric renal disease v1.111 MYO1E Eleanor Williams Phenotypes for gene: MYO1E were changed from to Glomerulosclerosis, focal segmental, 6 #614131
Proteinuric renal disease v1.110 MYO1E Eleanor Williams Publications for gene: MYO1E were set to PMID: 21697813
Proteinuric renal disease v1.109 MYH9 Eleanor Williams Phenotypes for gene: MYH9 were changed from to Epstein syndrome #153650; Fechtner syndrome #153640
Proteinuric renal disease v1.108 MYH9 Eleanor Williams Publications for gene: MYH9 were set to
Hereditary ataxia with onset in adulthood v1.171 MSTO1 Louise Daugherty Deleted their comment
Hereditary ataxia with onset in adulthood v1.171 PIK3R5 Louise Daugherty edited their review of gene: PIK3R5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from London North GLH and Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 PI4KA Louise Daugherty edited their review of gene: PI4KA: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 PCLO Louise Daugherty edited their review of gene: PCLO: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 SMPD4 Louise Daugherty edited their review of gene: SMPD4: Changed rating: AMBER
Hereditary ataxia with onset in adulthood v1.171 MME Louise Daugherty edited their review of gene: MME: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH and London North GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 KCNK18 Louise Daugherty edited their review of gene: KCNK18: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH and London North GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 CDK5 Louise Daugherty edited their review of gene: CDK5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 DCC Louise Daugherty edited their review of gene: DCC: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 DMXL2 Louise Daugherty edited their review of gene: DMXL2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 FRMD4A Louise Daugherty edited their review of gene: FRMD4A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 GLI3 Louise Daugherty edited their review of gene: GLI3: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 CCDC88C Louise Daugherty edited their review of gene: CCDC88C: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from London North GLH and Wessex and West Midlands GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.89 TBP Louise Daugherty edited their review of gene: TBP: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.89 TPK1 Louise Daugherty edited their review of gene: TPK1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.89 TREM2 Louise Daugherty edited their review of gene: TREM2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.89 TREX1 Louise Daugherty edited their review of gene: TREX1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.89 TREX1 Louise Daugherty Mode of inheritance for gene: TREX1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder v0.88 VPS37A Louise Daugherty edited their review of gene: VPS37A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 RNASEH2A Louise Daugherty edited their review of gene: RNASEH2A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 RNASEH2B Louise Daugherty edited their review of gene: RNASEH2B: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 RNASEH2C Louise Daugherty edited their review of gene: RNASEH2C: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SAMHD1 Louise Daugherty edited their review of gene: SAMHD1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED, there is relevance only to childhood onset; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SCN9A Louise Daugherty edited their review of gene: SCN9A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SCP2 Louise Daugherty edited their review of gene: SCP2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SDHAF1 Louise Daugherty edited their review of gene: SDHAF1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SLC41A1 Louise Daugherty edited their review of gene: SLC41A1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SLC46A1 Louise Daugherty edited their review of gene: SLC46A1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SNCAIP Louise Daugherty edited their review of gene: SNCAIP: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 SUOX Louise Daugherty edited their review of gene: SUOX: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED, more associated with childhood onset, which this panel does not represent.; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PTEN Louise Daugherty edited their review of gene: PTEN: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PSEN1 Louise Daugherty edited their review of gene: PSEN1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PPP2R2B Louise Daugherty edited their review of gene: PPP2R2B: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PNPT1 Louise Daugherty edited their review of gene: PNPT1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PDX1 Louise Daugherty edited their review of gene: PDX1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PDHX Louise Daugherty edited their review of gene: PDHX: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 PCDH12 Louise Daugherty edited their review of gene: PCDH12: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NUP62 Louise Daugherty Deleted their comment
Adult onset dystonia, chorea or related movement disorder v0.88 NUP62 Louise Daugherty commented on gene: NUP62: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Adult onset dystonia, chorea or related movement disorder v0.88 NUP62 Louise Daugherty edited their review of gene: NUP62: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NR4A2 Louise Daugherty edited their review of gene: NR4A2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NPC2 Louise Daugherty edited their review of gene: NPC2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NDUFS3 Louise Daugherty edited their review of gene: NDUFS3: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NDUFA9 Louise Daugherty edited their review of gene: NDUFA9: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NDUFA2 Louise Daugherty edited their review of gene: NDUFA2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 NDUFA12 Louise Daugherty edited their review of gene: NDUFA12: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 MR1 Louise Daugherty edited their review of gene: MR1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 MPV17 Louise Daugherty edited their review of gene: MPV17: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 MMADHC Louise Daugherty edited their review of gene: MMADHC: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 MCOLN1 Louise Daugherty edited their review of gene: MCOLN1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 MAT1A Louise Daugherty edited their review of gene: MAT1A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 L2HGDH Louise Daugherty edited their review of gene: L2HGDH: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 KCNK18 Louise Daugherty edited their review of gene: KCNK18: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH and London North GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 JPH3 Louise Daugherty edited their review of gene: JPH3: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR JPH3_CTG (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED.; Changed rating: RED
Rare multisystem ciliopathy disorders v1.100 KIAA0753 Eleanor Williams Phenotypes for gene: KIAA0753 were changed from Orofaciodigital syndrome XV 617127 to ?Orofaciodigital syndrome XV 617127; Short-rib skeletal dysplasia; Joubert syndrome
Rare multisystem ciliopathy disorders v1.99 KIAA0753 Eleanor Williams Publications for gene: KIAA0753 were set to 26643951
Rare multisystem ciliopathy disorders v1.98 KIAA0753 Eleanor Williams Classified gene: KIAA0753 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.98 KIAA0753 Eleanor Williams Added comment: Comment on list classification: 5 unrelated cases with homozygous or compound heterozygous variants in this gene and a ciliopathy-related phenotype.
Rare multisystem ciliopathy disorders v1.98 KIAA0753 Eleanor Williams Gene: kiaa0753 has been classified as Green List (High Evidence).
Adult onset dystonia, chorea or related movement disorder v0.88 IPPK Louise Daugherty edited their review of gene: IPPK: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 HTT Louise Daugherty edited their review of gene: HTT: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR HTT_CAG (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED.; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 HPRT1 Louise Daugherty Deleted their comment
Adult onset dystonia, chorea or related movement disorder v0.88 HPRT1 Louise Daugherty commented on gene: HPRT1: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Adult onset dystonia, chorea or related movement disorder v0.88 GIGYF2 Louise Daugherty commented on gene: GIGYF2: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Adult onset dystonia, chorea or related movement disorder v0.88 GAMT Louise Daugherty commented on gene: GAMT: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Adult onset dystonia, chorea or related movement disorder v0.88 FOXRED1 Louise Daugherty commented on gene: FOXRED1: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED
Adult onset dystonia, chorea or related movement disorder v0.88 FASTKD2 Louise Daugherty edited their review of gene: FASTKD2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 ERCC6 Louise Daugherty edited their review of gene: ERCC6: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 EARS2 Louise Daugherty edited their review of gene: EARS2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 DRD5 Louise Daugherty edited their review of gene: DRD5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 DRD2 Louise Daugherty edited their review of gene: DRD2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 DCAF10 Louise Daugherty edited their review of gene: DCAF10: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 BDNF Louise Daugherty edited their review of gene: BDNF: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 ATP6AP2 Louise Daugherty edited their review of gene: ATP6AP2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 HPRT1 Louise Daugherty edited their review of gene: HPRT1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 HEXA Louise Daugherty edited their review of gene: HEXA: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 GIGYF2 Louise Daugherty edited their review of gene: GIGYF2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 GAMT Louise Daugherty edited their review of gene: GAMT: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.88 FOXRED1 Louise Daugherty edited their review of gene: FOXRED1: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from South West GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Rare multisystem ciliopathy disorders v1.97 KIAA0753 Eleanor Williams commented on gene: KIAA0753
Primary lymphoedema v1.42 PIEZO1 Sarah Leigh Phenotypes for gene: PIEZO1 were changed from Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia to Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia
Primary lymphoedema v1.41 KIF11 Sarah Leigh Phenotypes for gene: KIF11 were changed from Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, 152950 to Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, MCLMR 152950
Primary lymphoedema v1.40 GJA1 Sarah Leigh Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia with primary lymphoedem 164200 to Oculodentodigital dysplasia 164200
Primary lymphoedema v1.39 GATA2 Sarah Leigh Added comment: Comment on phenotypes: Emberger syndrome (Primary Lymphedema with Myelodysplasia) 614038
Primary lymphoedema v1.39 GATA2 Sarah Leigh Phenotypes for gene: GATA2 were changed from Primary Lymphedema with Myelodysplasia (Emberger Syndrome) 614038 to Emberger Syndrome 614038; {Myelodysplastic syndrome, susceptibility to} 614286
Adult onset dystonia, chorea or related movement disorder v0.88 EARS2 Louise Daugherty Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924.; Dystonia to Combined oxidative phosphorylation deficiency 12, 614924; Dystonia
Adult onset dystonia, chorea or related movement disorder v0.87 C9orf72 Louise Daugherty edited their review of gene: C9orf72: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR C9orf72_GGGGCC (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.87 ATXN3 Louise Daugherty edited their review of gene: ATXN3: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR ATXN3_CAG (rated GREEN) and not the gene entity, as there are no SNVs for this gene being associated to the disorder, so this gene has been rated as RED.; Changed rating: RED
Adult onset dystonia, chorea or related movement disorder v0.87 ATXN2 Louise Daugherty edited their review of gene: ATXN2: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group as it is a RED gene on the Parkinson Disease and Complex Parkinsonism panel. It relates to the STR ATXN2_CAG and not the gene entity, as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Structural eye disease v0.76 FAT1 Nicola Ragge reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 30862798, 12724416 ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SMAD4 Nicola Ragge reviewed gene: SMAD4: Rating: AMBER; Mode of pathogenicity: ; Publications: 20735985, 11977156; Phenotypes: Myhre syndrome, 139210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRR12 Nicola Ragge reviewed gene: PRR12: Rating: GREEN; Mode of pathogenicity: ; Publications: 29556724; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 POMT2 Nicola Ragge reviewed gene: POMT2: Rating: AMBER; Mode of pathogenicity: ; Publications: 15894594, 28815891; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 POMT1 Nicola Ragge reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 12369018, 15037715; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, 236670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OLFM2 Nicola Ragge reviewed gene: OLFM2: Rating: AMBER; Mode of pathogenicity: ; Publications: 27844144; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MITF Nicola Ragge reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: ; Publications: 27889061; Phenotypes: COMMAD syndrome, 617306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KIAA1109 Nicola Ragge reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: ; Publications: 29290337, 617822; Phenotypes: Alkuraya-Kucinskas syndrome, ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ISPD Nicola Ragge reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: ; Publications: 22522421; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, 614643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IPO13 Nicola Ragge reviewed gene: IPO13: Rating: AMBER; Mode of pathogenicity: ; Publications: 29700284; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GLI2 Nicola Ragge reviewed gene: GLI2: Rating: AMBER; Mode of pathogenicity: ; Publications: 17096318, 21204792; Phenotypes: Holoprosencephaly 9, 610829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FKRP Nicola Ragge reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: ; Publications: 20236121, 15121789, 19955119, 20675713 ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 EFTUD2 Nicola Ragge reviewed gene: EFTUD2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26118977; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type, 610536; Mode of inheritance: mONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CPAMD8 Nicola Ragge reviewed gene: CPAMD8: Rating: GREEN; Mode of pathogenicity: ; Publications: 27839872; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ZIC2 Nicola Ragge reviewed gene: ZIC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 21976454; Phenotypes: Holoprosencephaly 5, 609637; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ZEB2 Nicola Ragge reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 16053902; Phenotypes: Mowat-Wilson syndrome (Hirschsprung disease with bilateral iris and retinal coloboma and high myopia), 235730; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ZEB1 Nicola Ragge reviewed gene: ZEB1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, posterior polymorphous, 3, Corneal dystrophy, Fuchs endothelial, 6, 609141, 613270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 WRN Nicola Ragge reviewed gene: WRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Werner syndrome , 277700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 VSX1 Nicola Ragge reviewed gene: VSX1: Rating: AMBER; Mode of pathogenicity: ; Publications: 15051220; Phenotypes: Corneal dystrophy, posterior polymorphous, 1, Keratoconus 1, Craniofacial anomalies and anterior segment dysgenesis syndrome, 122000, 148300, 614195; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 VIM Nicola Ragge reviewed gene: VIM: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 30, pulverulent, 116300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 UBIAD1 Nicola Ragge reviewed gene: UBIAD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, Schnyder type, 121800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TMX3 Nicola Ragge reviewed gene: TMX3: Rating: AMBER; Mode of pathogenicity: ; Publications: Chao et al 2010 PMID: 20485507; Phenotypes: Microphthalmia, coloboma, micrognathia, diaphragmatic hernia , None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TGFBI Nicola Ragge reviewed gene: TGFBI: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, epithelial basement membrane, Corneal dystrophy, Groenouw type I, Corneal dystrophy, lattice type I, Corneal dystrophy, Thiel-Behnke type, Corneal dystrophy, Avellino type, Corneal dystrophy, Reis-Bucklers type, Corneal dystrophy, lattice type IIIA, 121820, 121900, 122200, 602082, 607541, 608470, 608471; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TDRD7 Nicola Ragge reviewed gene: TDRD7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 36, 613887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCOF1 Nicola Ragge reviewed gene: TCOF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 8741923, 10888597; Phenotypes: Treacher Collins syndrome 1 (eyelid coloboma), 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TBX22 Nicola Ragge reviewed gene: TBX22: Rating: RED; Mode of pathogenicity: ; Publications: 22784330; Phenotypes: ?Abruzzo-Erickson syndrome, 302905; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 TBC1D32 Nicola Ragge reviewed gene: TBC1D32: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 24285566; Phenotypes: Orofaciodigital syndrome 9, 258865; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TACSTD2 Nicola Ragge reviewed gene: TACSTD2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, gelatinous drop-like, 204870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SRD5A3 Nicola Ragge reviewed gene: SRD5A3: Rating: GREEN; Mode of pathogenicity: ; Publications: PubMed: 20637498, 20700148, 26219881; Phenotypes: Kahrizi Syndrome (mental retardation, cataract, coloboma, kyphosis), 612713; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SMCHD1 Nicola Ragge reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 28067909, 28067911; Phenotypes: ARHINIA, CHOANAL ATRESIA, AND MICROPHTHALMIA, 603457; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SLC4A4 Nicola Ragge reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: 10545938, 11274232; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, 604278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC4A11 Nicola Ragge reviewed gene: SLC4A11: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal endothelial dystrophy and perceptive deafness, Corneal endothelial dystrophy 2, autosomal recessive, Corneal dystrophy, Fuchs endothelial, 4, 217400, 217700, 613268; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC38A8 Nicola Ragge reviewed gene: SLC38A8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis, 609218; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC33A1 Nicola Ragge reviewed gene: SLC33A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital cataracts, hearing loss, and neurodegeneration, 614482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC2A1 Nicola Ragge reviewed gene: SLC2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: STOMATIN-DEFICIENT CRYOHYDROCYTOSIS WITH NEUROLOGIC DEFECTS, 608885; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SLC16A12 Nicola Ragge reviewed gene: SLC16A12: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract, juvenile, with microcornea and glucosuria, 612018; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SIL1 Nicola Ragge reviewed gene: SIL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Marinesco-Sjogren syndrome, 248800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SH3PXD2B Nicola Ragge reviewed gene: SH3PXD2B: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 20137777, 29100834 ; Phenotypes: Frank-ter Haar syndrome, 249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SEMA3E Nicola Ragge reviewed gene: SEMA3E: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CHARGE, 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SEC23A Nicola Ragge reviewed gene: SEC23A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Craniolenticulosutural dysplasia, 607812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SCLT1 Nicola Ragge reviewed gene: SCLT1: Rating: GREEN; Mode of pathogenicity: ; Publications: PubMed:24285566, 29450879; Phenotypes: Orofaciodigital syndrome IX (a severe ciliopathy phenotype featuring midline cleft, microcephaly, and colobomatous microphthalmia/anophthalmia, one case only (Adly et al 2014), variant was classified as unknown significance by OMIM), None; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SC5D Nicola Ragge reviewed gene: SC5D: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: LATHOSTEROLOSIS, 607330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SALL1 Nicola Ragge reviewed gene: SALL1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 9973281, PMID: 16088922, PMID: 17221874; Phenotypes: Townes-Brocks branchiootorenal-like syndrome, 107480; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PXDN Nicola Ragge reviewed gene: PXDN: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 24939590, 21907015, 29450879; Phenotypes: Corneal opacification and other ocular anomalies, 269400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PTCH1 Nicola Ragge reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 16024850, 17001668; Phenotypes: Holoprosencephaly 7 (can include microphthalmia), 610828; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRDM5 Nicola Ragge reviewed gene: PRDM5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Brittle cornea syndrome 2, 614170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PQBP1 Nicola Ragge reviewed gene: PQBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 17033686; Phenotypes: Renpenning syndrome (can include microphthalmia/coloboma), 309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 POLR1D Nicola Ragge reviewed gene: POLR1D: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher-Collins Syndrome 2, 613717; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 POLR1C Nicola Ragge reviewed gene: POLR1C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher-Collins Syndrome, 248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PIKFYVE Nicola Ragge reviewed gene: PIKFYVE: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal fleck dystrophy, 121850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PEX6 Nicola Ragge reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4B, 614863; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX5 Nicola Ragge reviewed gene: PEX5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 2B, 202370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX3 Nicola Ragge reviewed gene: PEX3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger), 603164; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX26 Nicola Ragge reviewed gene: PEX26: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7B, 614873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX2 Nicola Ragge reviewed gene: PEX2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), Peroxisome biogenesis disorder 5B, 614866, 614867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX19 Nicola Ragge reviewed gene: PEX19: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger), 614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX16 Nicola Ragge reviewed gene: PEX16: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 8B, 614877; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX14 Nicola Ragge reviewed gene: PEX14: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger), 614887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX13 Nicola Ragge reviewed gene: PEX13: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 11B, 614885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX12 Nicola Ragge reviewed gene: PEX12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3B, 266510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX11B Nicola Ragge reviewed gene: PEX11B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 14B, 614920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX10 Nicola Ragge reviewed gene: PEX10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6B, 614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6D Nicola Ragge reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID:24166846; Phenotypes: ?Joubert syndrome 22 (microphthalmia/optic nerve coloboma, intrauterine growth retardation, facial dysmorphism, postaxial polydactyly of feet, syndactyly, polydactyly, renal hypoplasia, extinguished electroretinogram), 615665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PAX3 Nicola Ragge reviewed gene: PAX3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Waardenburg syndrome, type 3, Waardenburg syndrome, type 1, 148820, 193500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 P3H2 Nicola Ragge reviewed gene: P3H2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: MYOPIA, HIGH, WITH CATARACT AND VITREORETINAL DEGENERATION, 614292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OCRL Nicola Ragge reviewed gene: OCRL: Rating: AMBER; Mode of pathogenicity: ; Publications: 19168822; Phenotypes: Lowe syndrome, 309000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 NOTCH2 Nicola Ragge reviewed gene: NOTCH2: Rating: RED; Mode of pathogenicity: ; Publications: 22173065; Phenotypes: Hajdu-Cheney syndrome, Alagille syndrome 2, 102500, 610205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 NHS Nicola Ragge reviewed gene: NHS: Rating: GREEN; Mode of pathogenicity: ; Publications: 28922055, 23566852, 17417607 ; Phenotypes: Cataract 40, X-linked, Nance-Horan syndrome, 302200, 302350; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 NF2 Nicola Ragge reviewed gene: NF2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Neurofibromatosis, Type II, 101000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MYH9 Nicola Ragge reviewed gene: MYH9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Epstein Syndrome, Fechtner syndrome, 153650, 153640 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MIR184 Nicola Ragge reviewed gene: MIR184: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: EDICT syndrome, 614303; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MIP Nicola Ragge reviewed gene: MIP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 15, multiple types, 615274; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MAN2B1 Nicola Ragge reviewed gene: MAN2B1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mannosidosis, alpha-, types I and II, 248500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LMX1B Nicola Ragge reviewed gene: LMX1B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nail-patella syndrome, 161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 LIM2 Nicola Ragge reviewed gene: LIM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 19, 615277; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LCAT Nicola Ragge reviewed gene: LCAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Fish-eye disease, Norum disease, 136120, 245900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LAMB2 Nicola Ragge reviewed gene: LAMB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 30778388, 30120985, 28683731, 28188379, 27130041, 29450879; Phenotypes: Pierson syndrome, Nephrotic syndrome, type 5, with or without ocular abnormalities, 609049, 614199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KRT3 Nicola Ragge reviewed gene: KRT3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Meesmann corneal dystrophy, 122100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KRT12 Nicola Ragge reviewed gene: KRT12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Meesmann corneal dystrophy, 122100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KMT2D Nicola Ragge reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Kabuki syndrome 1 (can include coloboma), 147920, add review paper; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KERA Nicola Ragge reviewed gene: KERA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cornea plana congenita, recessive, 217300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KAT6B Nicola Ragge reviewed gene: KAT6B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: SBBYSS syndrome (blepharophimosis), 603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 JAM3 Nicola Ragge reviewed gene: JAM3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ITPR1 Nicola Ragge reviewed gene: ITPR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Gillespie syndrome, 206700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ITPA Nicola Ragge reviewed gene: ITPA: Rating: RED; Mode of pathogenicity: ; Publications: 26224535; Phenotypes: Warburg Micro syndrome and Martsolf syndrome with variable cardiac manifestation, None; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 HSF4 Nicola Ragge reviewed gene: HSF4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 5, multiple types, 116800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GSN Nicola Ragge reviewed gene: GSN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Amyloidosis, Finnish type, 105120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GNPTG Nicola Ragge reviewed gene: GNPTG: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucolipidosis III gamma, Retinitis Pigmentosa and skeletal abnormalities, 252605; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GJA8 Nicola Ragge reviewed gene: GJA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 1, multiple types, 116200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GJA3 Nicola Ragge reviewed gene: GJA3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 14, multiple types, 601885; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GFER Nicola Ragge reviewed gene: GFER: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay, 613076; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GCNT2 Nicola Ragge reviewed gene: GCNT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 13 with adult i phenotype, 116700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GALT Nicola Ragge reviewed gene: GALT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Galactosemia, 230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GALK1 Nicola Ragge reviewed gene: GALK1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Galactokinase deficiency with cataracts, 230200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FZD5 Nicola Ragge reviewed gene: FZD5: Rating: AMBER; Mode of pathogenicity: ; Publications: Liu et al 2016 PMID: 26908622; Phenotypes: Coloboma, None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FYCO1 Nicola Ragge reviewed gene: FYCO1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 18, autosomal recessive, 610019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FTL Nicola Ragge reviewed gene: FTL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperferritinemia-cataract syndrome, 600886; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FOXL2 Nicola Ragge reviewed gene: FOXL2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Blepharophimosis, epicanthus inversus, and ptosis, 110100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FNBP4 Nicola Ragge reviewed gene: FNBP4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Microphthalmia with Limb anomalies (Classified as variant of unknown significance on OMIM), 206920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FBN1 Nicola Ragge reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 1301946, 8136837; Phenotypes: Ectopia lentis, familial, Marfan syndrome, MASS syndrome, Weill-Marchesani syndrome 2, dominant, Marfan lipodystrophy syndrome, 129600, 154700, 604308, 608328, 616914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FAM126A Nicola Ragge reviewed gene: FAM126A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: LEUKODYSTROPHY, HYPOMYELINATING, 5 (includes congenital cataract), 610532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FAM111A Nicola Ragge reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Kenny-Caffey syndrome, type 2, Gracile bone dysplasia, 127000, 602361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FADD Nicola Ragge reviewed gene: FADD: Rating: RED; Mode of pathogenicity: ; Publications: Gregory-Evans et al, 2007 PMID: 17656375 ; Phenotypes: Iris coloboma, retinal coloboma , None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EYA1 Nicola Ragge reviewed gene: EYA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Anterior segment anomalies with or without cataract, Branchiootic syndrome 1, 113650, 602588; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EPHA2 Nicola Ragge reviewed gene: EPHA2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 6, multiple types, 116600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EPG5 Nicola Ragge reviewed gene: EPG5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Vici syndrome, 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DPYD Nicola Ragge reviewed gene: DPYD: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Dihydropyrimidine dehydrogenase deficiency , 274270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DHX38 Nicola Ragge reviewed gene: DHX38: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis Pigmentosa and Macular Coloboma, 618220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DHCR7 Nicola Ragge reviewed gene: DHCR7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Smith-Lemli-Opitz syndrome, 270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DCN Nicola Ragge reviewed gene: DCN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, congenital stromal, 610048; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CYP51A1 Nicola Ragge reviewed gene: CYP51A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.76 CTDP1 Nicola Ragge reviewed gene: CTDP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, 604168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYGS Nicola Ragge reviewed gene: CRYGS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 20, multiple types, 116100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYGD Nicola Ragge reviewed gene: CRYGD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 4, Multiple Types, 115700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYGC Nicola Ragge reviewed gene: CRYGC: Rating: GREEN; Mode of pathogenicity: ; Publications: 24281366, 29386872; Phenotypes: Cataract 2, multiple types (often with microcornea), 604307; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYGB Nicola Ragge reviewed gene: CRYGB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 39, multiple types, autosomal dominant, 615188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYBB3 Nicola Ragge reviewed gene: CRYBB3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 22, autosomal recessive, 609741; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYBB2 Nicola Ragge reviewed gene: CRYBB2: Rating: AMBER; Mode of pathogenicity: ; Publications: 29386872; Phenotypes: Cataract 3, multiple types, 601547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYBB1 Nicola Ragge reviewed gene: CRYBB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 29386872; Phenotypes: Cataract 17, multiple types, 611544; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYBA4 Nicola Ragge reviewed gene: CRYBA4: Rating: AMBER; Mode of pathogenicity: ; Publications: 16960806, 20577656 ; Phenotypes: Cataract 23 (and microphthalmia in 1 case), 610425; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYBA1 Nicola Ragge reviewed gene: CRYBA1: Rating: RED; Mode of pathogenicity: ; Publications: 26303524; Phenotypes: Cataract 10, multiple types, 600881; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRYAB Nicola Ragge reviewed gene: CRYAB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CATARACT 16, MULTIPLE TYPES, 613763; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 CRYAA Nicola Ragge reviewed gene: CRYAA: Rating: GREEN; Mode of pathogenicity: ; Publications: 17296897, 30340470 , 18302245 ; Phenotypes: Cataract 9, multiple types (some patients also have microphthalmia and/or microcornea), 604219; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRIM1 Nicola Ragge reviewed gene: CRIM1: Rating: AMBER; Mode of pathogenicity: ; Publications: 26681494, 25561690; Phenotypes: Macrophthalmia, Colobomatous, with microcornea, 602499; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 COL8A2 Nicola Ragge reviewed gene: COL8A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, Fuchs endothelial, 1, Corneal dystrophy, posterior polymorphous 2, 136800, 609140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 COL18A1 Nicola Ragge reviewed gene: COL18A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17546652, 22399687; Phenotypes: Knobloch syndrome, type 1, 267750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHST6 Nicola Ragge reviewed gene: CHST6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Macular corneal dystrophy, 217800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHRDL1 Nicola Ragge reviewed gene: CHRDL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22284829; Phenotypes: Megalocornea 1, X-linked, 309300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 CHMP4B Nicola Ragge reviewed gene: CHMP4B: Rating: RED; Mode of pathogenicity: ; Publications: 17701905; Phenotypes: Cataract 31, multiple types, 605387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CBS Nicola Ragge reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: ; Publications: 7611293, 24169224, 21626167, 11774777; Phenotypes: Homocystinuria, B6-responsive and nonresponsive types (includes ectopia lentis), 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BFSP2 Nicola Ragge reviewed gene: BFSP2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 12, multiple types, 611597; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BFSP1 Nicola Ragge reviewed gene: BFSP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataract 33, 611391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 ALDH18A1 Nicola Ragge reviewed gene: ALDH18A1: Rating: RED; Mode of pathogenicity: ; Publications: 21739576; Phenotypes: Cutis laxa, autosomal recessive, type IIIA, 219150; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 AGPS Nicola Ragge reviewed gene: AGPS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3, 600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AGK Nicola Ragge reviewed gene: AGK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Sengers syndrome, Cataract 38, autosomal recessive, 212350, 614691; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AGBL1 Nicola Ragge reviewed gene: AGBL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Corneal dystrophy, Fuchs endothelial, 8, 615523; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ADAMTSL4 Nicola Ragge reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: ; Publications: 20702823, 20141359, 25975359 ; Phenotypes: Ectopia lentis, isolated, autosomal recessive, Ectopia lentis et pupillae, 225100, 225200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADAMTS18 Nicola Ragge reviewed gene: ADAMTS18: Rating: GREEN; Mode of pathogenicity: ; Publications: 23818446; Phenotypes: Microcornea, myopic chorioretinal atrophy, and telecanthus, 615458; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ZNF513 Nicola Ragge reviewed gene: ZNF513: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 58, 613617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ZNF423 Nicola Ragge reviewed gene: ZNF423: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 19, Nephronophthisis 14, 614844, 614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 XPC Nicola Ragge reviewed gene: XPC: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C, 278720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 XPA Nicola Ragge reviewed gene: XPA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A, 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 WT1 Nicola Ragge reviewed gene: WT1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: WILMS TUMOR,ANIRIDIA, GENITOURINARY ANOMALIES, AND MENTAL RETARDATION SYNDROME, 194072; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 WHRN Nicola Ragge reviewed gene: WHRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 2D, 611383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 WFS1 Nicola Ragge reviewed gene: WFS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Wolfram syndrome, Wolfram-like syndrome, autosomal dominant, ?Cataract 41, 222300, 614296, 116400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 WDR36 Nicola Ragge reviewed gene: WDR36: Rating: RED; Mode of pathogenicity: ; Publications: 17353431, 18172102, 15677485; Phenotypes: Glaucoma 1, open angle, G, 609887; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 WDPCP Nicola Ragge reviewed gene: WDPCP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Bardet-Biedl syndrome 15, 615992; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 VCAN Nicola Ragge reviewed gene: VCAN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Wagner syndrome 1, 143200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 VAX1 Nicola Ragge reviewed gene: VAX1: Rating: AMBER; Mode of pathogenicity: ; Publications: 10601035, 22095910; Phenotypes: Microphthalmia, syndromic 11, 614402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 USH2A Nicola Ragge reviewed gene: USH2A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 39, Usher syndrome type 2A, 613809, 276901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 USH1G Nicola Ragge reviewed gene: USH1G: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 1G, 606943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 USH1C Nicola Ragge reviewed gene: USH1C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Deafness, autosomal recessive 18A, Usher syndrome type 1C, 602092, 276904; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 UNC119 Nicola Ragge reviewed gene: UNC119: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy, Immunodeficiency 13, , 615518; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TYRP1 Nicola Ragge reviewed gene: TYRP1: Rating: RED; Mode of pathogenicity: ; Publications: 10644000; Phenotypes: Albinism, oculocutaneous, type III, [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)], 203290, 612271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TYR Nicola Ragge reviewed gene: TYR: Rating: RED; Mode of pathogenicity: ; Publications: 28778995; Phenotypes: Albinism, oculocutaneous, type IA, Albinism, oculocutaneous, type IB, Waardenburg syndrome/albinism, digenic, [Skin/hair/eye pigmentation 3, blue/green eyes], [Skin/hair/eye pigmentation 3, light/dark/freckling skin], {Melanoma, cutaneous malignant, susceptibility to, 8}, 203100, 606952, 103470, 601800, 601800, 601800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 TULP1 Nicola Ragge reviewed gene: TULP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 15, Retinitis pigmentosa 14, 613843, 600132; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TTC8 Nicola Ragge reviewed gene: TTC8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 51, Bardet-Biedl syndrome 8, 613464, 615985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TTC21B Nicola Ragge reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: SHORT-RIB THORACIC DYSPLASIA 4 WITH OR WITHOUT POLYDACTYLY, 613819; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TSPAN12 Nicola Ragge reviewed gene: TSPAN12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Exudative vitreoretinopathy 5, 613310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TRPM1 Nicola Ragge reviewed gene: TRPM1: Rating: RED; Mode of pathogenicity: other - please provide details in the comments; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1C, autosomal recessive, 613216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TRIM44 Nicola Ragge reviewed gene: TRIM44: Rating: RED; Mode of pathogenicity: ; Publications: 26394807; Phenotypes: ANIRIDIA 3, 617142; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TRIM32 Nicola Ragge reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 11, Muscular dystrophy, limb-girdle, type 2H, 615988, 254110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TPP1 Nicola Ragge reviewed gene: TPP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 2, 204500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TP53BP2 Nicola Ragge reviewed gene: TP53BP2: Rating: RED; Mode of pathogenicity: ; Publications: 28150229, 27447114, ; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.76 TOPORS Nicola Ragge reviewed gene: TOPORS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 31, 609923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TMEM67 Nicola Ragge reviewed gene: TMEM67: Rating: GREEN; Mode of pathogenicity: ; Publications: 19058225, 30055837 ; Phenotypes: COACH syndrome, Joubert syndrome 6, Meckel syndrome 3, Nephronophthisis 11, {Bardet-Biedl syndrome 14, modifer of}, 216360, 610688, 607361, 613550, 615991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM237 Nicola Ragge reviewed gene: TMEM237: Rating: GREEN; Mode of pathogenicity: ; Publications: 22152675, 30055837 ; Phenotypes: Joubert syndrome 14, 614424; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM231 Nicola Ragge reviewed gene: TMEM231: Rating: RED; Mode of pathogenicity: ; Publications: 23012439, 23349226; Phenotypes: Joubert syndrome 20, Meckel syndrome 11, 614970, 615397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM216 Nicola Ragge reviewed gene: TMEM216: Rating: GREEN; Mode of pathogenicity: ; Publications: 20512146, 30055837; Phenotypes: Joubert syndrome 2, Meckel syndrome 2, 608091, 603194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM138 Nicola Ragge reviewed gene: TMEM138: Rating: RED; Mode of pathogenicity: ; Publications: 22282472; Phenotypes: Joubert syndrome 16, 614465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM126A Nicola Ragge reviewed gene: TMEM126A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Optic atrophy, 612989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TIMP3 Nicola Ragge reviewed gene: TIMP3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Sorsby fundus dystrophy, 136900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TIMM8A Nicola Ragge reviewed gene: TIMM8A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mohr-Tranebjaerg syndrome, 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 TFAP2A Nicola Ragge reviewed gene: TFAP2A: Rating: GREEN; Mode of pathogenicity: ; Publications: 18423521, 19685247 ; Phenotypes: Branchiooculofacial syndrome (includes ocular anomalies such as microphthalmia and lacrimal duct obstruction), 113620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 TENM3 Nicola Ragge reviewed gene: TENM3: Rating: GREEN; Mode of pathogenicity: ; Publications: 22766609, 27103084, 24859618, 29753094, 30513139; Phenotypes: Microphthalmia, isolated, with coloboma 9, 615145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCTN3 Nicola Ragge reviewed gene: TCTN3: Rating: RED; Mode of pathogenicity: ; Publications: 25118024, 29725084; Phenotypes: Joubert syndrome 18, Orofaciodigital syndrome IV, 614815, 258860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCTN2 Nicola Ragge reviewed gene: TCTN2: Rating: RED; Mode of pathogenicity: ; Publications: 21565611, 25118024; Phenotypes: Meckel syndrome 8, Joubert syndrome 24, 613885, 616654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TCTN1 Nicola Ragge reviewed gene: TCTN1: Rating: RED; Mode of pathogenicity: ; Publications: 21725307, 22693042; Phenotypes: Joubert syndrome 13, 614173; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SPINT2 Nicola Ragge reviewed gene: SPINT2: Rating: RED; Mode of pathogenicity: ; Publications: 29575628, 24142340, ; Phenotypes: DIARRHEA 3, SECRETORY SODIUM, CONGENITAL, WITH OR WITHOUT OTHER CONGENITAL ANOMALIES, 270420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SPATA7 Nicola Ragge reviewed gene: SPATA7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 3, Retinitis pigmentosa, juvenile, autosomal recessive, 604232, 604232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SNRNP200 Nicola Ragge reviewed gene: SNRNP200: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 33, 610359; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SLC45A2 Nicola Ragge reviewed gene: SLC45A2: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Albinism, oculocutaneous, type IV, [Skin/hair/eye pigmentation 5, black/nonblack hair], [Skin/hair/eye pigmentation 5, dark/fair skin], [Skin/hair/eye pigmentation 5, dark/light eyes] , 606574, 227240, 227240, 227240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC24A5 Nicola Ragge reviewed gene: SLC24A5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ALBINISM, OCULOCUTANEOUS, TYPE VI, 113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SLC24A1 Nicola Ragge reviewed gene: SLC24A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1D, autosomal recessive, 613830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SIX3 Nicola Ragge reviewed gene: SIX3: Rating: AMBER; Mode of pathogenicity: ; Publications: 21976454, 10369266, 21940735; Phenotypes: Holoprosencephaly 2, , 157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SEMA4A Nicola Ragge reviewed gene: SEMA4A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 35, Cone-rod dystrophy 10, 610282, 610283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 SDCCAG8 Nicola Ragge reviewed gene: SDCCAG8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Senior-Loken syndrome 7, Bardet-Biedl syndrome 16, 613615, 615993; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SALL2 Nicola Ragge reviewed gene: SALL2: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24412933; Phenotypes: Coloboma, ocular, autosomal recessive, 216820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SAG Nicola Ragge reviewed gene: SAG: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Oguchi disease-1, Retinitis pigmentosa 47, 258100, 613758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RS1 Nicola Ragge reviewed gene: RS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinoschisis, 312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 RPGRIP1 Nicola Ragge reviewed gene: RPGRIP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 13, Leber congenital amaurosis 6, 608194, 613826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RPGR Nicola Ragge reviewed gene: RPGR: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 3, Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, Macular degeneration, X-linked atrophic, Cone-rod dystrophy, X-linked, 1 , 300029, 300455, 300834, 304020; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 RPE65 Nicola Ragge reviewed gene: RPE65: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 2, 204100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RP9 Nicola Ragge reviewed gene: RP9: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ?Retinitis pigmentosa 9, 180104; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RP2 Nicola Ragge reviewed gene: RP2: Rating: RED; Mode of pathogenicity: ; Publications: 21738648; Phenotypes: Retinitis pigmentosa 2, 312600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 RP1 Nicola Ragge reviewed gene: RP1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 1, 180100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ROM1 Nicola Ragge reviewed gene: ROM1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 7, digenic, 608133; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RLBP1 Nicola Ragge reviewed gene: RLBP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bothnia retinal dystrophy, Newfoundland rod-cone dystrophy, Fundus albipunctatus, 607475, 607476, 136880; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RIMS1 Nicola Ragge reviewed gene: RIMS1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: 28677725; Phenotypes: Cone-rod dystrophy 7, 603649; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RHO Nicola Ragge reviewed gene: RHO: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 4, autosomal dominant or recessive, Night blindness, congenital stationary, autosomal dominant 1, , 613731, 610445, 136880; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RGS9BP Nicola Ragge reviewed gene: RGS9BP: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Bradyopsia, 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RGS9 Nicola Ragge reviewed gene: RGS9: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Bradyopsia, 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RGR Nicola Ragge reviewed gene: RGR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 44, 613769; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 RDH5 Nicola Ragge reviewed gene: RDH5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Fundus albipunctatus, 136880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RDH12 Nicola Ragge reviewed gene: RDH12: Rating: RED; Mode of pathogenicity: ; Publications: 25148430, 22065924; Phenotypes: Leber congenital amaurosis 13, 612712; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RD3 Nicola Ragge reviewed gene: RD3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 12, 610612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RBP3 Nicola Ragge reviewed gene: RBP3: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ?Retinitis pigmentosa 66, 615233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RAX2 Nicola Ragge reviewed gene: RAX2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 11, Macular degeneration, age-related, 6, 610381, 613757; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPH2 Nicola Ragge reviewed gene: PRPH2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis punctata albescens, Macular dystrophy, patterned, 1, Leber congenital amaurosis 18, Macular dystrophy, vitelliform, 3, Choriodal dystrophy, central areolar 2 , 136880, 169150, 608133, 608161, 613105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PRPF8 Nicola Ragge reviewed gene: PRPF8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 13, 600059; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPF6 Nicola Ragge reviewed gene: PRPF6: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 60, 613983; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPF31 Nicola Ragge reviewed gene: PRPF31: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 11, 600138; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PRPF3 Nicola Ragge reviewed gene: PRPF3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 18, 601414; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PROM1 Nicola Ragge reviewed gene: PROM1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Stargardt disease 4, Macular dystrophy, retinal, 2, Retinitis pigmentosa 41, Cone-rod dystrophy 12, 603786, 608051, 612095, 612657; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PRCD Nicola Ragge reviewed gene: PRCD: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 36, 610599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PPT1 Nicola Ragge reviewed gene: PPT1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 1, 256730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 POLH Nicola Ragge reviewed gene: POLH: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, VARIANT TYPE, 278750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PLA2G5 Nicola Ragge reviewed gene: PLA2G5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: [Fleck retina, familial benign], 228980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PITX3 Nicola Ragge reviewed gene: PITX3: Rating: GREEN; Mode of pathogenicity: ; Publications: 20033184, 29405783, 9620774; Phenotypes: Anterior segment mesenchymal dysgenesis, Cataract 11, multiple types, 107250, 610623; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PITPNM3 Nicola Ragge reviewed gene: PITPNM3: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Cone-rod dystrophy 5, 600977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 PHYH Nicola Ragge reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Refsum disease, 266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PEX7 Nicola Ragge reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Rhizomelic chondrodysplasia punctata, type 1, Peroxisome biogenesis disorder 9B, 215100, 614879; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDZD7 Nicola Ragge reviewed gene: PDZD7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type IIC, GPR98/PDZD7 digenic, Retinal disease in Usher syndrome type IIA, modifier of, 605472, 276901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6H Nicola Ragge reviewed gene: PDE6H: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Achromatopsia 6, 610024; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6G Nicola Ragge reviewed gene: PDE6G: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 57, 613582; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6C Nicola Ragge reviewed gene: PDE6C: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone dystrophy 4, 613093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6B Nicola Ragge reviewed gene: PDE6B: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Night blindness, congenital stationary, autosomal dominant 2, Retinitis pigmentosa-40, 163500, 613801; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 PDE6A Nicola Ragge reviewed gene: PDE6A: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Retinitis pigmentosa 43, 613810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PCDH15 Nicola Ragge reviewed gene: PCDH15: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Usher syndrome, type 1D/F digenic, Usher syndrome, type 1F, Deafness, autosomal recessive 23, 601067, 602083, 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OPTN Nicola Ragge reviewed gene: OPTN: Rating: RED; Mode of pathogenicity: ; Publications: 11834836; Phenotypes: Glaucoma 1, open angle, E, 137760; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 OPA3 Nicola Ragge reviewed gene: OPA3: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Optic atrophy 3 with cataract, 165300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 OPA1 Nicola Ragge reviewed gene: OPA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Optic atrophy plus syndrome, Optic atrophy 1, Behr syndrome, Glaucoma, normal tension, susceptibility to, , 125250, 165500, 210000, ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 OFD1 Nicola Ragge reviewed gene: OFD1: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: 28173652; Phenotypes: Joubert syndrome 10, ?Retinitis pigmentosa 23, 300804, 300424; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 OCA2 Nicola Ragge reviewed gene: OCA2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Albinism, brown oculocutaneous, Albinism oculocutaneous, type II, [Skin/hair/eye pigmentation 1, blond/brown hair], [Skin/hair/eye pigmentation 1, blue/nonblue eyes], 203200, 203200, 227220, 227220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 OAT Nicola Ragge reviewed gene: OAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Gyrate atrophy of choroid and retina with or without ornithinemia, 258870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NYX Nicola Ragge reviewed gene: NYX: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1A, X-linked, 310500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 NTF4 Nicola Ragge reviewed gene: NTF4: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: GLAUCOMA 1, OPEN ANGLE, O, 613100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 NRL Nicola Ragge reviewed gene: NRL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 27, 613750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 NR2E3 Nicola Ragge reviewed gene: NR2E3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 37, Enhanced S-cone syndrome, 611131, 268100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 NPHP4 Nicola Ragge reviewed gene: NPHP4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronophthisis 4, Senior-Loken syndrome 4, 606966, 606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NPHP3 Nicola Ragge reviewed gene: NPHP3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronophthisis 3, Meckel syndrome 7, Renal-hepatic-pancreatic dysplasia 1, 604387, 267010, 208540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NPHP1 Nicola Ragge reviewed gene: NPHP1: Rating: RED; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Nephronophthisis 1, juvenile, Senior-Loken syndrome-1, Joubert syndrome 4, 256100, 266900, 609583; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 NDP Nicola Ragge reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 26130484, 29617172, 29321361, 17334993; Phenotypes: Exudative vitreoretinopathy 2, X-linked, Norrie disease, 305390, 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 NAA10 Nicola Ragge reviewed gene: NAA10: Rating: GREEN; Mode of pathogenicity: other - please provide details in the comments; Publications: 24431331, 30842225; Phenotypes: Microphthalmia, syndromic 1, 309800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 MYO7A Nicola Ragge reviewed gene: MYO7A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 1B, Deafness, autosomal recessive 2, Deafness, autosomal dominant 11, 276900, 601317; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 MTTP Nicola Ragge reviewed gene: MTTP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Abetalipoproteinemia, 200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MPLKIP Nicola Ragge reviewed gene: MPLKIP: Rating: RED; Mode of pathogenicity: ; Publications: 21959366; Phenotypes: TRICHOTHIODYSTROPHY 4, NONPHOTOSENSITIVE, 234050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MKS1 Nicola Ragge reviewed gene: MKS1: Rating: RED; Mode of pathogenicity: ; Publications: 23454480; Phenotypes: Bardet-Biedl syndrome 13, Meckel syndrome 1, 615990, 249000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MKKS Nicola Ragge reviewed gene: MKKS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 6, McKusick-Kaufman syndrome, 605231, 236700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MIR204 Nicola Ragge reviewed gene: MIR204: Rating: AMBER; Mode of pathogenicity: ; Publications: 26056285; Phenotypes: RETINAL DYSTROPHY AND IRIS COLOBOMA WITH OR WITHOUT CONGENITAL CATARACT, 616722; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 MFSD8 Nicola Ragge reviewed gene: MFSD8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 7, MACULAR DYSTROPHY WITH CENTRAL CONE INVOLVEMENT, 610951, 616170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MFN2 Nicola Ragge reviewed gene: MFN2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 2A2, 609260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MERTK Nicola Ragge reviewed gene: MERTK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 38, 613862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MAK Nicola Ragge reviewed gene: MAK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 62, 614181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LZTFL1 Nicola Ragge reviewed gene: LZTFL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome 17, 615994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LRP5 Nicola Ragge reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: ; Publications: 29131652, 28111184, 20034086; Phenotypes: Osteoporosis-pseudoglioma syndrome, Exudative vitreoretinopathy 4, Osteopetrosis, autosomal dominant 1, van Buchem disease, type 2, 259770, 601813, 607634, ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 LRMDA Nicola Ragge reviewed gene: LRMDA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ALBINISM, OCULOCUTANEOUS, TYPE VII, 615179; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LRIT3 Nicola Ragge reviewed gene: LRIT3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1F, autosomal recessive, 615058; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LRAT Nicola Ragge reviewed gene: LRAT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 14, 613341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 LCA5 Nicola Ragge reviewed gene: LCA5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 5, 604537; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KLHL7 Nicola Ragge reviewed gene: KLHL7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 42, 612943; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 KIF7 Nicola Ragge reviewed gene: KIF7: Rating: RED; Mode of pathogenicity: ; Publications: 21633164; Phenotypes: Acrocallosal syndrom (JOUBERT SYNDROME 12), 200990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KCTD7 Nicola Ragge reviewed gene: KCTD7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: EPILEPSY, PROGRESSIVE MYOCLONIC, 3, WITH OR WITHOUT INTRACELLULAR INCLUSIONS, 611726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KCNV2 Nicola Ragge reviewed gene: KCNV2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinal cone dystrophy 3B, 610356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 KCNJ13 Nicola Ragge reviewed gene: KCNJ13: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 16, Snowflake vitreoretinal degeneration, 614186, 193230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 IQCB1 Nicola Ragge reviewed gene: IQCB1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Senior-Loken syndrome 5: an autosomal recessive disorder with the main features of nephronophthisis (NPHP, see 256100) and Leber congenital amaurosis (LCA, see 204000)., 609254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 INVS Nicola Ragge reviewed gene: INVS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronophthisis 2, infantile, 602088; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 INPP5E Nicola Ragge reviewed gene: INPP5E: Rating: GREEN; Mode of pathogenicity: ; Publications: 23386033, 30055837, 23022135; Phenotypes: Joubert syndrome 1, Mental retardation, truncal obesity, retinal dystrophy, and micropenis, 213300, 610156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IMPG2 Nicola Ragge reviewed gene: IMPG2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 56, Macular dystrophy, vitelliform, 5, 613581, 616152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IMPDH1 Nicola Ragge reviewed gene: IMPDH1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 10, Leber congenital amaurosis 11, 180105, 613837; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 IDH3B Nicola Ragge reviewed gene: IDH3B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 46, 612572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 HMGB3 Nicola Ragge reviewed gene: HMGB3: Rating: AMBER; Mode of pathogenicity: ; Publications: 24993872, ; Phenotypes: ?Microphthalmia, syndromic 13, 300915; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 HDAC6 Nicola Ragge reviewed gene: HDAC6: Rating: RED; Mode of pathogenicity: other - please provide details in the comments; Publications: 20181727; Phenotypes: CHONDRODYSPLASIA WITH PLATYSPONDYLY, DISTINCTIVE BRACHYDACTYLY, HYDROCEPHALY, AND MICROPHTHALMIA, 300863; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 HARS Nicola Ragge reviewed gene: HARS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome type 3B, Charcot-Marie-Tooth disease, axonal, type 2W, 614504, 616625; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 GUCY2D Nicola Ragge reviewed gene: GUCY2D: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Leber congenital amaurosis 1, Cone-rod dystrophy 6, 204000, 601777; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 GUCA1B Nicola Ragge reviewed gene: GUCA1B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 48, 613827; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GUCA1A Nicola Ragge reviewed gene: GUCA1A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone dystrophy-3, 602093; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GTF2H5 Nicola Ragge reviewed gene: GTF2H5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: TRICHOTHIODYSTROPHY 3, PHOTOSENSITIVE, 616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GRN Nicola Ragge reviewed gene: GRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 11, 614706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GRM6 Nicola Ragge reviewed gene: GRM6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1B, autosomal recessive, 257270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GPR179 Nicola Ragge reviewed gene: GPR179: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1E, autosomal recessive, 614565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GPR143 Nicola Ragge reviewed gene: GPR143: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Nystagmus 6, congenital, X-linked, Ocular albinism, type I, Nettleship-Falls type, 300814, 300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 GNAT2 Nicola Ragge reviewed gene: GNAT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Achromatopsia-4, 613856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GNAT1 Nicola Ragge reviewed gene: GNAT1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary, autosomal dominant 3, ?Night blindness, congenital stationary, type 1G, 610444, 616389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 GDF6 Nicola Ragge reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: 17236135, 20494911, 25457163, 24033328, 21070663; Phenotypes: KLIPPEL-FEIL SYNDROME 1(includes microphthalmia), Microphthalmia with coloboma6, digenic (with GDF3), Microphthalmia, isolated 4 , 118100 , 613703 , 613094 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 GDF3 Nicola Ragge reviewed gene: GDF3: Rating: AMBER; Mode of pathogenicity: other - please provide details in the comments; Publications: 19864492; Phenotypes: Klippel-Feil Syndrome3, Microphthalmia with coloboma 6, Microphthalmia, isolated 7, 613702, 613703, 613704; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FZD4 Nicola Ragge reviewed gene: FZD4: Rating: AMBER; Mode of pathogenicity: ; Publications: 28413837, 30882657; Phenotypes: Exudative vitreoretinopathy 1, 133780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FSCN2 Nicola Ragge reviewed gene: FSCN2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 30, 607921; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 FLVCR1 Nicola Ragge reviewed gene: FLVCR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ataxia, posterior column, with retinitis pigmentosa, 609033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 FAM161A Nicola Ragge reviewed gene: FAM161A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 28, 606068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 EYS Nicola Ragge reviewed gene: EYS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 25, 602772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC8 Nicola Ragge reviewed gene: ERCC8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cockayne syndrome, type A, 216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC6 Nicola Ragge reviewed gene: ERCC6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cerebrooculofacioskeletal syndrome 1, Macular degeneration, age-related, susceptibility to 5, 214150, 613761; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC5 Nicola Ragge reviewed gene: ERCC5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Xeroderma Pigmentosum, group G (includes microphthalmia and/or cataract), Cerebrooculofacioskeletal syndrome 3, 278780, 616570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC4 Nicola Ragge reviewed gene: ERCC4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F, 278760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC3 Nicola Ragge reviewed gene: ERCC3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: TRICHOTHIODYSTROPHY 2, PHOTOSENSITIVE, 616390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC2 Nicola Ragge reviewed gene: ERCC2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: TRICHOTHIODYSTROPHY 1, PHOTOSENSITIVE, 601675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ERCC1 Nicola Ragge reviewed gene: ERCC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 17273966; Phenotypes: Cerebrooculofacioskeletal syndrome 4 (includes microphthalmia), 610758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ELP4 Nicola Ragge reviewed gene: ELP4: Rating: RED; Mode of pathogenicity: ; Publications: 24290376, 29217025; Phenotypes: ANIRIDIA 2, 617141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ELOVL4 Nicola Ragge reviewed gene: ELOVL4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Stargardt disease 3, 600110; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 EFEMP1 Nicola Ragge reviewed gene: EFEMP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Doyne honeycomb degeneration of retina, 126600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 DHDDS Nicola Ragge reviewed gene: DHDDS: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 59, 613861; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DDB2 Nicola Ragge reviewed gene: DDB2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP E, 278740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 DDB1 Nicola Ragge reviewed gene: DDB1: Rating: RED; Mode of pathogenicity: ; Publications: 17129780; Phenotypes: ; Mode of inheritance:
Structural eye disease v0.76 CYP4V2 Nicola Ragge reviewed gene: CYP4V2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bietti crystalline corneoretinal dystrophy, 210370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CYP27A1 Nicola Ragge reviewed gene: CYP27A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEREBROTENDINOUS XANTHOMATOSIS, 213700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CTSD Nicola Ragge reviewed gene: CTSD: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 10, 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CRX Nicola Ragge reviewed gene: CRX: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod retinal dystrophy-2, Leber congenital amaurosis 7, 120970, 613829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CRB1 Nicola Ragge reviewed gene: CRB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 21484995, 23077403; Phenotypes: Leber congenital amaurosis 8, Retinitis pigmentosa-12, autosomal recessive, Pigmented paravenous chorioretinal atrophy, 613835, 600105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 COL9A2 Nicola Ragge reviewed gene: COL9A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: STICKLER SYNDROME, TYPE V, 614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 COL9A1 Nicola Ragge reviewed gene: COL9A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, type IV, 614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 COL2A1 Nicola Ragge reviewed gene: COL2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 18541977, 17347327; Phenotypes: Vitreoretinopathy with phalangeal epiphyseal dysplasia, Stickler syndrome, type I, Epiphyseal dysplasia, multiple, with myopia and deafness, Kniest dysplasia, SED congenita, Stickler sydrome, type I, nonsyndromic ocular, , , 108300, 156550, 609508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 COL11A2 Nicola Ragge reviewed gene: COL11A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 COL11A1 Nicola Ragge reviewed gene: COL11A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, type II, Marshall syndrome, 604841, 154780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 CNNM4 Nicola Ragge reviewed gene: CNNM4: Rating: AMBER; Mode of pathogenicity: ; Publications: 27419834; Phenotypes: Jalili syndrome, 217080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGB3 Nicola Ragge reviewed gene: CNGB3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Macular degeneration, juvenile, Achromatopsia-3, 248200, 262300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGB1 Nicola Ragge reviewed gene: CNGB1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 45, 613767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGA3 Nicola Ragge reviewed gene: CNGA3: Rating: RED; Mode of pathogenicity: ; Publications: 24504161; Phenotypes: Achromatopsia-2, 216900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CNGA1 Nicola Ragge reviewed gene: CNGA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 49, 613756; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLRN1 Nicola Ragge reviewed gene: CLRN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 3A, Retinitis pigmentosa 61, 276902, 614180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN8 Nicola Ragge reviewed gene: CLN8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, 600143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN6 Nicola Ragge reviewed gene: CLN6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, 601780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN5 Nicola Ragge reviewed gene: CLN5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, 256731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CLN3 Nicola Ragge reviewed gene: CLN3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 3, 204200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CIB2 Nicola Ragge reviewed gene: CIB2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type IJ, 614869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CHM Nicola Ragge reviewed gene: CHM: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Choroideremia, 303100; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 CERKL Nicola Ragge reviewed gene: CERKL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 26, 608380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CEP41 Nicola Ragge reviewed gene: CEP41: Rating: RED; Mode of pathogenicity: ; Publications: 22246503; Phenotypes: Joubert syndrome 15, 614464; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CEP290 Nicola Ragge reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: ; Publications: 30055837, 22355252; Phenotypes: Joubert syndrome 5, Senior-Loken syndrome 6, Meckel syndrome 4, Leber congenital amaurosis 10, ?Bardet-Biedl syndrome 14, 610188, 610189, 611134, 611755, 615991; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CDHR1 Nicola Ragge reviewed gene: CDHR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 15, 613660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CDH3 Nicola Ragge reviewed gene: CDH3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy, Hypotrichosis, congenital, with juvenile macular dystrophy, 225280, 601553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CDH23 Nicola Ragge reviewed gene: CDH23: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 1D, 601067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CACNA2D4 Nicola Ragge reviewed gene: CACNA2D4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinal cone dystrophy 4, 610478; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CACNA1F Nicola Ragge reviewed gene: CACNA1F: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (incomplete), 2A, X-linked, Cone-rod dystropy, X-linked, 3, Aland Island eye disease, 300071, 300476, 300600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v0.76 CABP4 Nicola Ragge reviewed gene: CABP4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Night blindness, congenital stationary (incomplete), 2B, autosomal recessive, 610427; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 CA4 Nicola Ragge reviewed gene: CA4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 17, 600852; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 C8orf37 Nicola Ragge reviewed gene: C8orf37: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 16, 614500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C5orf42 Nicola Ragge reviewed gene: C5orf42: Rating: RED; Mode of pathogenicity: ; Publications: 24178751; Phenotypes: Joubert syndrome 17, 614615; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C2orf71 Nicola Ragge reviewed gene: C2orf71: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinitis pigmentosa 54, 613428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 C1QTNF5 Nicola Ragge reviewed gene: C1QTNF5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinal degeneration, late-onset, autosomal dominant, 605670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BMPR1A Nicola Ragge reviewed gene: BMPR1A: Rating: AMBER; Mode of pathogenicity: ; Publications: 29522511; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BMP7 Nicola Ragge reviewed gene: BMP7: Rating: AMBER; Mode of pathogenicity: other - please provide details in the comments; Publications: 20506283, 7590254; Phenotypes: Microphthalmia, anophthalmia, systemic abnormalities, intellectual disability, None; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BEST1 Nicola Ragge reviewed gene: BEST1: Rating: GREEN; Mode of pathogenicity: ; Publications: 15452077, 21473666 ; Phenotypes: Vitelliform Macular degeneration 2, Microcornea, rod-cone dystrophy, cataract, and posterior, staphyloma, Bestrophinopathy, autosomal recessive, Retinitis pigmentosa, concentric , 153700, 193220, 611809, 613194; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 BBS9 Nicola Ragge reviewed gene: BBS9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome9, 615986; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS7 Nicola Ragge reviewed gene: BBS7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome7, 615984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS5 Nicola Ragge reviewed gene: BBS5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome5, 615983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS4 Nicola Ragge reviewed gene: BBS4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome4, 615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS2 Nicola Ragge reviewed gene: BBS2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome2, Retinitis pigmentosa 74, 615981, 616562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS12 Nicola Ragge reviewed gene: BBS12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome12, 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS10 Nicola Ragge reviewed gene: BBS10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome10, 615987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 BBS1 Nicola Ragge reviewed gene: BBS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Bardet-Biedl syndrome1, 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 B3GLCT Nicola Ragge reviewed gene: B3GLCT: Rating: GREEN; Mode of pathogenicity: ; Publications: 16909395; Phenotypes: Peters-plus syndrome, 261540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ATP13A2 Nicola Ragge reviewed gene: ATP13A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: KUFOR-RAKEB SYNDROME, SPASTIC PARAPLEGIA 78, AUTOSOMAL RECESSIVE, 606693, 617225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ATOH7 Nicola Ragge reviewed gene: ATOH7: Rating: GREEN; Mode of pathogenicity: ; Publications: 1838, 8779, 22068589, 11493566 ; Phenotypes: Persistent hyperplastic primary vitreous, autosomal recessive (can include microphthalmia), 221900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ASB10 Nicola Ragge reviewed gene: ASB10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: GLAUCOMA 1, OPEN ANGLE, F, 603383; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ARL6 Nicola Ragge reviewed gene: ARL6: Rating: RED; Mode of pathogenicity: ; Publications: 19097054; Phenotypes: Retinitis pigmentosa 55, Bardet-Biedl syndrome 3, {Bardet-Biedl syndrome 1, modifier of}, 613575, 600151, 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ARL13B Nicola Ragge reviewed gene: ARL13B: Rating: RED; Mode of pathogenicity: ; Publications: 18674751, 25138100; Phenotypes: Joubert syndrome 8, 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ALMS1 Nicola Ragge reviewed gene: ALMS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Alstrom syndrome, 203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AIPL1 Nicola Ragge reviewed gene: AIPL1: Rating: AMBER; Mode of pathogenicity: ; Publications: 25148430; Phenotypes: Cone-rod dystrophy, Leber congenital amaurosis 4, Retinitis pigmentosa, juvenile, 604393, 604393, 604393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 AHI1 Nicola Ragge reviewed gene: AHI1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Joubert syndrome 3, 608629; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADGRV1 Nicola Ragge reviewed gene: ADGRV1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Usher syndrome, type 2C, 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ADAM9 Nicola Ragge reviewed gene: ADAM9: Rating: RED; Mode of pathogenicity: ; Publications: 25091951; Phenotypes: Cone-rod dystrophy 9, 612775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ABHD12 Nicola Ragge reviewed gene: ABHD12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract , 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 ABCB6 Nicola Ragge reviewed gene: ABCB6: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: 22226084; Phenotypes: Microphthalmia, isolated, with coloboma 7, 614497; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 ABCA4 Nicola Ragge reviewed gene: ABCA4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Cone-rod dystrophy 3, Fundus flavimaculatus, Retinal dystrophy, early-onset severe, Retinitis pigmentosa 19, Stargardt disease 1, {Macular degeneration, age-related, 2}, 604116, 248200, 248200, 601718, 248200, 153800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 TUBGCP4 Nicola Ragge reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 25817018; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SBF2 Nicola Ragge reviewed gene: SBF2: Rating: GREEN; Mode of pathogenicity: ; Publications: 12687498, 15304601; Phenotypes: Charcot-Marie-Tooth disease, type 4B2 604563, CMT with early onset glaucoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RBP4 Nicola Ragge reviewed gene: RBP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 9888420, 27892788, 25910211 ; Phenotypes: Retinal dystrophy, iris coloboma, and comedogenic acne syndrome, 615147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 PIGL Nicola Ragge reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: ; Publications: 22444671; Phenotypes: CHIME syndrome, 280000, Coloboma, Congenital Heart Disease, Ichthyosiform Dermatosis,Mental Retardation, and Ear Anomalies Syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 MAF Nicola Ragge reviewed gene: MAF: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 12642301, 17982426, 16470690; Phenotypes: Cataract 21, multiple types 610202; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 LRP2 Nicola Ragge reviewed gene: LRP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 17632512, 8266995, 18553518; Phenotypes: Donnai-Barrow syndrome, 222448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 IGBP1 Nicola Ragge reviewed gene: IGBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 14556245; Phenotypes: Corpus callosum, agenesis of, with mental retardation, ocular coloboma andmicrognathia, 300472; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v0.76 HMX1 Nicola Ragge reviewed gene: HMX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 18423520, 21417677, 25574057, 29140751; Phenotypes: Oculoauricular syndrome 612109; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v0.76 GJA1 Nicola Ragge reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 21273537, 25976645, 15637728, 24508941, 30628995; Phenotypes: Oculodentodigital dysplasia, open angle glaucoma (OAG) and microcornea; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 DDX58 Nicola Ragge reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: ; Publications: 25620203, 30574673; Phenotypes: Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 YAP1 Nicola Ragge reviewed gene: YAP1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 24462371, 27267789, 28801591 ; Phenotypes: isolated ocular coloboma, Coloboma, ocular, 120433, Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mentalretardation, 120433; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 VSX2 Nicola Ragge reviewed gene: VSX2: Rating: GREEN; Mode of pathogenicity: ; Publications: 10932181, 20414678 ; Phenotypes: Microphthalmia with coloboma 3, 610092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 TMEM98 Nicola Ragge reviewed gene: TMEM98: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 26392740, 24852644; Phenotypes: NNO4, Nanophthalmos 4, 615972; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 TBC1D20 Nicola Ragge reviewed gene: TBC1D20: Rating: GREEN; Mode of pathogenicity: ; Publications: 24239381; Phenotypes: Warburg micro syndrome 4, 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 STRA6 Nicola Ragge reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: ; Publications: 17273977, 24859618; Phenotypes: Syndromic Microphthalmia, Recessive, Microphthalmia, isolated, with coloboma 8, 601186, Microphthalmia, syndromic 9, 601186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SOX2 Nicola Ragge reviewed gene: SOX2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 12612584, 24859618; Phenotypes: Microphthalmia, syndromic 3 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 SMOC1 Nicola Ragge reviewed gene: SMOC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21194678, 21194680, 30445150; Phenotypes: Microphthalmia with limb anomalies, 206920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 SMO Nicola Ragge reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 27236920; Phenotypes: Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 SIX6 Nicola Ragge reviewed gene: SIX6: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 23167593, 24702266, 29450879, 15266624; Phenotypes: Microphthalmia with cataract 2, 212550, Optic disc anomalies with retinal and/or macular dystrophy, 212550, Anophthalmia/Microphthalmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown - Change
Structural eye disease v0.76 SHH Nicola Ragge reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: ; Publications: 12503095, 20425842; Phenotypes: Holoprosencephaly-3, 142945, Microphthalmia with coloboma 5, 611638, Single median maxillary central incisor, 147250, Schizencephaly, 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v0.76 SALL4 Nicola Ragge reviewed gene: SALL4: Rating: GREEN; Mode of pathogenicity: ; Publications: 12843316, 6426304; Phenotypes: Duane-radial ray syndrome, 607323; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v0.76 RPGRIP1L Nicola Ragge reviewed gene: RPGRIP1L: Rating: GREEN; Mode of pathogenicity: ; Publications: 19574260; Phenotypes: COACH syndrome, 216360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v0.76 RAX Nicola Ragge reviewed gene: RAX: Rating: GREEN; Mode of pathogenicity: ; Publications: 14662654, 18783408, 24033328; Phenotypes: Anophthalmia/Microphthalmia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal