| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intellectual disability v3.499 | METTL5 | Arina Puzriakova Phenotypes for gene: METTL5 were changed from Autosomal-Recessive Intellectual Disability and Microcephaly; Delayed speech and language development; Intellectual disability; Microcephaly; Behavioral abnormality to Intellectual developmental disorder, autosomal recessive 72, 618665 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.498 | METTL5 | Arina Puzriakova Tag for-review tag was added to gene: METTL5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.498 | METTL5 | Arina Puzriakova reviewed gene: METTL5: Rating: ; Mode of pathogenicity: None; Publications: 29302074, 31564433; Phenotypes: Intellectual developmental disorder, autosomal recessive 72, 618665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.498 | MFSD2A | Arina Puzriakova Classified gene: MFSD2A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.498 | MFSD2A | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated Green at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.498 | MFSD2A | Arina Puzriakova Gene: mfsd2a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.497 | MFSD2A | Arina Puzriakova Phenotypes for gene: MFSD2A were changed from NA to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities, 616486 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.496 | MFSD2A | Arina Puzriakova Publications for gene: MFSD2A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.495 | MFSD2A | Arina Puzriakova Mode of inheritance for gene: MFSD2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.494 | MFSD2A | Arina Puzriakova Tag for-review tag was added to gene: MFSD2A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.494 | MFSD2A | Arina Puzriakova reviewed gene: MFSD2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005868, 26005865, 29302074, 30043326, 32572202; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities, 616486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.494 | NPHP3 | Arina Puzriakova Publications for gene: NPHP3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.493 | NPHP3 | Arina Puzriakova Classified gene: NPHP3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.493 | NPHP3 | Arina Puzriakova Added comment: Comment on list classification: Kept rating Amber as affected individuals are more likely to be assessed under renal and ciliopathy panels, for which this gene is already Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.493 | NPHP3 | Arina Puzriakova Gene: nphp3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.492 | NPHP3 | Arina Puzriakova reviewed gene: NPHP3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 3, 604387, Renal-hepatic-pancreatic dysplasia 1, 208540, Meckel syndrome 7, 267010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.492 | ZIC1 | Arina Puzriakova Publications for gene: ZIC1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.491 | ZIC1 |
Arina Puzriakova changed review comment from: Associated with phenotype in OMIM, and a 'confirmed' gene for Craniosynostosis 6 in Gene2Phenotype. At least 5 variants reported in 6 unrelated families with intellectual disability (2 mild, 1 moderate, 2 moderate-severe, 1 severe) among other variable CNS abnormalities including craniosynostosis, callosal dysgenesis, anomaly in cerebellar hemispheres, vermis and pons, spinal dysraphism, as well as skull abnormalities not associated with craniosynostosis. ; to: Associated with phenotype in OMIM, and a 'confirmed' gene for Craniosynostosis 6 in Gene2Phenotype. At least 5 variants reported in 6 unrelated families with intellectual disability (2 mild, 1 moderate, 2 moderate-severe, 1 severe) among other variable CNS abnormalities including craniosynostosis, callosal dysgenesis, anomaly in cerebellar hemispheres, vermis and pons, spinal dysraphism, as well as skull abnormalities not associated with craniosynostosis. Predicted that both gain- and loss-of-function variants can be deleterious. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.491 | ZIC1 |
Arina Puzriakova changed review comment from: Associated with phenotype in OMIM, and a 'confirmed' gene for Craniosynostosis 6 in Gene2Phenotype. At least 5 variants reported in 6 unrelated families with craniosynostosis and associated variable intellectual disability (2 mild, 1 moderate, 2 moderate-severe, 1 severe); to: Associated with phenotype in OMIM, and a 'confirmed' gene for Craniosynostosis 6 in Gene2Phenotype. At least 5 variants reported in 6 unrelated families with intellectual disability (2 mild, 1 moderate, 2 moderate-severe, 1 severe) among other variable CNS abnormalities including craniosynostosis, callosal dysgenesis, anomaly in cerebellar hemispheres, vermis and pons, spinal dysraphism, as well as skull abnormalities not associated with craniosynostosis. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.491 | ZIC1 | Arina Puzriakova Phenotypes for gene: ZIC1 were changed from CRANIOSYNOSTOSIS 6 to Structural brain anomalies with impaired intellectual development and craniosynostosis, 618736; ?Craniosynostosis 6, 616602 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.490 | ZIC1 | Arina Puzriakova Classified gene: ZIC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.490 | ZIC1 | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated Green at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.490 | ZIC1 | Arina Puzriakova Gene: zic1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.489 | ZIC1 | Arina Puzriakova Tag for-review tag was added to gene: ZIC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.489 | ZIC1 | Arina Puzriakova reviewed gene: ZIC1: 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: 26340333, 30391508; Phenotypes: ?Craniosynostosis 6, 616602, Structural brain anomalies with impaired intellectual development and craniosynostosis, 618736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.489 | ZNF335 | Arina Puzriakova Publications for gene: ZNF335 were set to 23178126 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.488 | ZNF335 | Arina Puzriakova Classified gene: ZNF335 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.488 | ZNF335 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated Green at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.488 | ZNF335 | Arina Puzriakova Gene: znf335 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.487 | ZNF335 |
Arina Puzriakova Tag watchlist was removed from gene: ZNF335. Tag for-review tag was added to gene: ZNF335. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.487 | ZNF335 | Arina Puzriakova commented on gene: ZNF335: Removed 'watchlist' tag as there are now sufficient cases to support a gene-disease association, and for this gene to be rated Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.487 | ZNF335 | Arina Puzriakova reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 23178126, 27540107, 29652087, 30500859, 31187448; Phenotypes: Microcephaly 10, primary, autosomal recessive, 615095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.487 | ZNF335 | Arina Puzriakova Phenotypes for gene: ZNF335 were changed from ?Microcephaly 10, primary, autosomal recessive, 615095; developmental delay; intellectual disability to Microcephaly 10, primary, autosomal recessive, 615095 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.486 | ZNF335 | Arina Puzriakova Mode of inheritance for gene: ZNF335 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.485 | ZNF148 | Arina Puzriakova reviewed gene: ZNF148: Rating: AMBER; Mode of pathogenicity: None; Publications: 27964749; Phenotypes: Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, 617260; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.485 | KIF21B | Arina Puzriakova Classified gene: KIF21B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.485 | KIF21B | Arina Puzriakova Added comment: Comment on list classification: Rating Amber, but should be promoted to Green at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.485 | KIF21B | Arina Puzriakova Gene: kif21b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | KIF21B | Arina Puzriakova Tag for-review tag was added to gene: KIF21B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | KIF21B | Arina Puzriakova commented on gene: KIF21B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | COX6B1 | Zornitza Stark reviewed gene: COX6B1: Rating: RED; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | SCO1 | Zornitza Stark reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | PRKACB |
Konstantinos Varvagiannis gene: PRKACB was added gene: PRKACB was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKACB were set to 33058759 Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability Penetrance for gene: PRKACB were set to unknown Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to AMBER Added comment: ID was a feature in 2/4 individuals with PRKACB pathogenic variant reported to date. Please consider inclusion of PRKACB (and PRKACA) in other relevant gene panels e.g. for polydactyly, congenital heart defects. The disorder may be considered in the DD of ciliopathies. ----- Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants. The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD. Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors. Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID. As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes. WES was carried out in all. PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD). PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo. Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt). By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals. As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | FA2H | Sarah Leigh Tag for-review tag was added to gene: FA2H. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | FA2H | Sarah Leigh reviewed gene: FA2H: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.484 | CDH2 | Sarah Leigh Phenotypes for gene: CDH2 were changed from Abnormality of the corpus callosum; Abnormality of neuronal migration; Bimanual synkinesia; Duane anomaly; Abnormality of cardiovascular system; Abnormality of the eye; Abnormality of the genital system; Global developmental delay; Intellectual disability to Agenesis of corpus callosum, cardiac, ocular, and genital syndrome 618929 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | CDH2 | Sarah Leigh Tag for-review tag was added to gene: CDH2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | CDH2 | Sarah Leigh reviewed gene: CDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | SCN8A | Arina Puzriakova Tag for-review tag was added to gene: SCN8A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | SCN8A | Arina Puzriakova commented on gene: SCN8A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | PIGP | Arina Puzriakova Tag for-review tag was added to gene: PIGP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | PIGP | Arina Puzriakova Classified gene: PIGP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | PIGP | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.483 | PIGP | Arina Puzriakova Gene: pigp has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.482 | PUM1 | Arina Puzriakova Classified gene: PUM1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.482 | PUM1 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.482 | PUM1 | Arina Puzriakova Gene: pum1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.481 | PUM1 | Arina Puzriakova Tag for-review tag was added to gene: PUM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.481 | RALGAPA1 | Arina Puzriakova Classified gene: RALGAPA1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.481 | RALGAPA1 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.481 | RALGAPA1 | Arina Puzriakova Gene: ralgapa1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.480 | RALGAPA1 | Arina Puzriakova Tag for-review tag was added to gene: RALGAPA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.480 | RARS | Arina Puzriakova Classified gene: RARS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.480 | RARS | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.480 | RARS | Arina Puzriakova Gene: rars has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.479 | RARS | Arina Puzriakova Tag for-review tag was added to gene: RARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.479 | RNF113A | Arina Puzriakova Classified gene: RNF113A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.479 | RNF113A | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.479 | RNF113A | Arina Puzriakova Gene: rnf113a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.478 | RNF113A | Arina Puzriakova Tag for-review tag was added to gene: RNF113A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.478 | RNF13 | Arina Puzriakova Classified gene: RNF13 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.478 | RNF13 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.478 | RNF13 | Arina Puzriakova Gene: rnf13 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.477 | RNF13 | Arina Puzriakova Tag for-review tag was added to gene: RNF13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.477 | GAD1 | Arina Puzriakova Classified gene: GAD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.477 | GAD1 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.477 | GAD1 | Arina Puzriakova Gene: gad1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.476 | GAD1 | Arina Puzriakova Tag for-review tag was added to gene: GAD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.476 | CEP55 | Arina Puzriakova Classified gene: CEP55 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.476 | CEP55 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.476 | CEP55 | Arina Puzriakova Gene: cep55 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.475 | CEP55 | Arina Puzriakova Tag for-review tag was added to gene: CEP55. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.475 | CTU2 | Arina Puzriakova Classified gene: CTU2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.475 | CTU2 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.475 | CTU2 | Arina Puzriakova Gene: ctu2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.474 | CTU2 | Arina Puzriakova Tag for-review tag was added to gene: CTU2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.474 | ALG9 | Arina Puzriakova Classified gene: ALG9 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.474 | ALG9 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.474 | ALG9 | Arina Puzriakova Gene: alg9 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.473 | ALG9 | Arina Puzriakova Tag for-review tag was added to gene: ALG9. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.473 | EXT2 | Arina Puzriakova Classified gene: EXT2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.473 | EXT2 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.473 | EXT2 | Arina Puzriakova Gene: ext2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.472 | EXT2 | Arina Puzriakova Tag for-review tag was added to gene: EXT2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.472 | PTRHD1 | Arina Puzriakova Classified gene: PTRHD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.472 | PTRHD1 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.472 | PTRHD1 | Arina Puzriakova Gene: ptrhd1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.471 | PTRHD1 | Arina Puzriakova Tag for-review tag was added to gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.471 | TRAPPC4 | Arina Puzriakova Classified gene: TRAPPC4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.471 | TRAPPC4 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.471 | TRAPPC4 | Arina Puzriakova Gene: trappc4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.470 | TRAPPC4 | Arina Puzriakova Tag for-review tag was added to gene: TRAPPC4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.470 | UGP2 | Arina Puzriakova Classified gene: UGP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.470 | UGP2 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.470 | UGP2 | Arina Puzriakova Gene: ugp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.469 | CXorf56 | Arina Puzriakova Classified gene: CXorf56 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.469 | CXorf56 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.469 | CXorf56 | Arina Puzriakova Gene: cxorf56 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.468 | KAT8 | Arina Puzriakova Classified gene: KAT8 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.468 | KAT8 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.468 | KAT8 | Arina Puzriakova Gene: kat8 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.467 | SLC5A6 | Arina Puzriakova Classified gene: SLC5A6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.467 | SLC5A6 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.467 | SLC5A6 | Arina Puzriakova Gene: slc5a6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.466 | SNX27 | Arina Puzriakova Classified gene: SNX27 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.466 | SNX27 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.466 | SNX27 | Arina Puzriakova Gene: snx27 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | UGP2 | Arina Puzriakova Tag for-review tag was added to gene: UGP2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | CXorf56 | Arina Puzriakova Tag for-review tag was added to gene: CXorf56. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | KAT8 | Arina Puzriakova Tag for-review tag was added to gene: KAT8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | SLC5A6 | Arina Puzriakova Tag for-review tag was added to gene: SLC5A6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | SNX27 | Arina Puzriakova Tag for-review tag was added to gene: SNX27. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | WNT1 | Arina Puzriakova Classified gene: WNT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | WNT1 | Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.465 | WNT1 | Arina Puzriakova Gene: wnt1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.464 | WNT1 | Arina Puzriakova Tag for-review tag was added to gene: WNT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.464 | PIGK | Arina Puzriakova Classified gene: PIGK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.464 | PIGK | Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.464 | PIGK | Arina Puzriakova Gene: pigk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.463 | PIGK | Arina Puzriakova Tag for-review tag was added to gene: PIGK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.463 | HSPG2 | Ivone Leong Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, type 1, 255800; Dyssegmental dysplasia, Silverman-Handmaker type, 224410 to Schwartz-Jampel syndrome, type 1, 255800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.462 | KDM3B | Ivone Leong commented on gene: KDM3B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.462 | KCNMA1 | Ivone Leong Publications for gene: KCNMA1 were set to 15937479; 31427379; 31152168; 27567911 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.461 | KCNK4 | Ivone Leong Tag watchlist tag was added to gene: KCNK4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.461 | KCNK4 | Ivone Leong commented on gene: KCNK4: As the 2 unrelated patients who have the same de novo variants have severe ID/DD and 3rd patient has low average ID, this gene will be kept as Amber until further evidence is available. Watchlist tag has been added as well. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.461 | IQSEC1 | Ivone Leong Tag watchlist tag was added to gene: IQSEC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.461 | LMBRD2 | Arina Puzriakova changed review comment from: Comment on list classification: There is a sufficient number of unrelated cases to rate this gene GREEN at the next major review.; to: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber but there is a sufficient number of unrelated cases with the relevant phenotype to rate this gene GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.461 | KCNK4 | Ivone Leong Phenotypes for gene: KCNK4 were changed from Neurodevelopmental delay; Intellectual disability; Seizures; Gingival overgrowth; Hypertrichosis to Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome, 618381 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.460 | IQSEC1 | Ivone Leong commented on gene: IQSEC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.460 | IQSEC1 | Ivone Leong Phenotypes for gene: IQSEC1 were changed from Central hypotonia; Global developmental delay; Intellectual disability; Behavioral abnormality; Short stature to Central hypotonia; Global developmental delay; Intellectual disability; Behavioral abnormality; Short stature; Intellectual developmental disorder with short stature and behavioral abnormalities, 618687 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.459 | ALG14 | Arina Puzriakova Classified gene: ALG14 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.459 | ALG14 | Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.459 | ALG14 | Arina Puzriakova Gene: alg14 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.458 | XYLT1 | Arina Puzriakova Publications for gene: XYLT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.457 | XYLT1 | Arina Puzriakova Phenotypes for gene: XYLT1 were changed from {Pseudoxanthoma elasticum, modifier of severity of}, 264800; Desbuquois dysplasia 2, 615777 to Desbuquois dysplasia 2, 615777 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | XYLT1 | Arina Puzriakova reviewed gene: XYLT1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Desbuquois dysplasia 2, 615777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | XYLT1 | Arina Puzriakova Tag for-review tag was added to gene: XYLT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | CSNK1G1 | Konstantinos Varvagiannis reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33009664; Phenotypes: Global developmental delay, Intellectual disability, Autism, Seizures, Abnormality of the face, Abnormality of limbs; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | LMNB2 |
Konstantinos Varvagiannis gene: LMNB2 was added gene: LMNB2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: LMNB2 were set to 33033404 Phenotypes for gene: LMNB2 were set to Congenital microcephaly; Global developmental delay; Intellectual disability Penetrance for gene: LMNB2 were set to Complete Mode of pathogenicity for gene: LMNB2 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: LMNB2 was set to GREEN Added comment: Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6). LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event. LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His. LMNB1/2 common phenotypes : All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) apart from one individual, without history of IUGR or postnatally abnormal height (the latter in most). Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2. LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13). LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occurred at the age of 6y in 1/6). Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some). Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some). Animal model: Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different. Variant effect : variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments. Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency. [Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed] Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | LMNB1 |
Konstantinos Varvagiannis edited their review of gene: LMNB1: Added comment: There is an additional report on LMBN1/2-associated phenotypes supporting green rating of the gene in the current panel. Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6). LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event. LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His. LMNB1/2 common phenotypes : All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most). Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2. LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13). LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6). Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some). Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some). Animal model: Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different. Variant effect : variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments. Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency. [Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]; Changed publications: 32910914, 33033404 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | CNPY3 | Arina Puzriakova Classified gene: CNPY3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | CNPY3 |
Arina Puzriakova Added comment: Comment on list classification: New gene added and reviewed by Konstantinos Varvagiannis. Although there are sufficient cases to support a gene-disease association, this disorder is mainly characterised by severe epileptic encephalopathy and ID manifests secondarily to seizures. Rating Amber, but this may be reviewed if new evidence emerges indicating that neurodevelopmental impairment precedes onset of seizures. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.456 | CNPY3 | Arina Puzriakova Gene: cnpy3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.455 | HSPG2 | Ivone Leong Publications for gene: HSPG2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.454 | USP7 | Arina Puzriakova Publications for gene: USP7 were set to 30679821; 26365382; 19946331 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.453 | USP7 | Arina Puzriakova Phenotypes for gene: USP7 were changed from Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism to Hao-Fountain syndrome, 616863 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.452 | USP7 | Arina Puzriakova Classified gene: USP7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.452 | USP7 | Arina Puzriakova Added comment: Comment on list classification: Based on published evidence and expert reviews, this gene should be promoted from Amber to Green at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.452 | USP7 | Arina Puzriakova Gene: usp7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.451 | USP7 | Arina Puzriakova Tag for-review tag was added to gene: USP7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.451 | USP7 | Arina Puzriakova reviewed gene: USP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26365382, 30679821, 33012787; Phenotypes: Hao-Fountain syndrome, 616863; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.451 | STT3A | Arina Puzriakova Classified gene: STT3A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.451 | STT3A |
Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to support a gene-disease association, and so STT3A should be promoted from Amber to Green at the next GMS panel update (added 'for-review' tag). ID/DD reported in all cases (at least 7 individuals from 3 unrelated families, with 2 different homozygous variants in STT3A) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.451 | STT3A | Arina Puzriakova Gene: stt3a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.450 | STT3A | Arina Puzriakova commented on gene: STT3A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.450 | STT3A | Arina Puzriakova Phenotypes for gene: STT3A were changed from ?Congenital disorder of glycosylation, type Iw, 615596; developmental delay; intellectual disability to Congenital disorder of glycosylation, type Iw, 615596 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.449 | STT3A | Arina Puzriakova Publications for gene: STT3A were set to 28424003; 23842455 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.448 | STT3A |
Arina Puzriakova Tag watchlist was removed from gene: STT3A. Tag for-review tag was added to gene: STT3A. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.448 | CARS2 |
Arina Puzriakova changed review comment from: Comment on list classification: Kept rating Amber as developmental regression and progressive cognitive decline appear secondary to seizures, which represent the key phenotypic feature of this disorder. This gene is Green on the Inborn errors of metabolism (v2.2) panel, a component the Epilepsy super panel, which should be a sufficient route for detecting these cases.; to: Comment on list classification: Kept rating Amber as developmental regression and progressive cognitive decline appear secondary to seizures, which represent the key phenotypic feature of this disorder. This gene is Green on Inborn errors of metabolism (v2.3) and has been added to the Genetic epilepsy syndromes (v2.176) panel, which should be sufficient routes for detecting these cases. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.448 | TRPM3 | Arina Puzriakova Classified gene: TRPM3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.448 | TRPM3 |
Arina Puzriakova Added comment: Comment on list classification: Excluding the individual harbouring a VUS, 8 unrelated individuals with ID and the same p.Val837Met variant have been reported (PMID:31278393, 32439617). Also now available is functional data demonstrating variants render the channel overactive. With addition of the recent publications, there is enough evidence to support a Green rating on this panel. Therefore added 'for-review' tag, for reassessment at next GMS panel update. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.448 | TRPM3 | Arina Puzriakova Gene: trpm3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.447 | TRPM3 | Arina Puzriakova Publications for gene: TRPM3 were set to 31278393 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.446 | TRPM3 | Arina Puzriakova Tag for-review tag was added to gene: TRPM3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.446 | TRPM3 | Arina Puzriakova reviewed gene: TRPM3: Rating: ; 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: 32439617, 32343227, 32427099; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.446 | FGF14 | Arina Puzriakova Classified gene: FGF14 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.446 | FGF14 |
Arina Puzriakova Added comment: Comment on list classification: Cognitive impairment has been reported in several patients, mostly mild but few cases with moderate deficits have also been described. However, the phenotype is mainly characterised by ataxia which would be the expected CI for diagnostic testing - FGF14 is already Green on Ataxia panels. The utility of calling variants in this gene in a cohort of ID patients without the ataxic component is unlikely to be of benefit, and therefore the rating has been kept Amber on this panel. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.446 | FGF14 | Arina Puzriakova Gene: fgf14 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.445 | FGF14 | Arina Puzriakova Publications for gene: FGF14 were set to 15470364 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.444 | FDFT1 | Arina Puzriakova Phenotypes for gene: FDFT1 were changed from Profound global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Cortical visual impairment; Abnormality of the skin; Abnormality of the face to Squalene synthase deficiency, 618156 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.443 | FDFT1 | Arina Puzriakova Tag watchlist tag was added to gene: FDFT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.443 | DENND5A | Arina Puzriakova Phenotypes for gene: DENND5A were changed from EPILEPTIC ENCEPHALOPATHY to Epileptic encephalopathy, early infantile, 49 617281 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.442 | DENND5A | Arina Puzriakova Classified gene: DENND5A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.442 | DENND5A |
Arina Puzriakova Added comment: Comment on list classification: Kept rating Amber as disorder is mainly characterised by severe early-infantile encephalopathy, and cognitive arrest appears secondary to the onset of seizures. This gene is Green on the Genetic epilepsy syndromes (v2.170) panel, which should be a sufficient route for detecting cases. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.442 | DENND5A | Arina Puzriakova Gene: dennd5a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.441 | CEP104 | Arina Puzriakova changed review comment from: Four related cases reported (PMID:26477546 and 31625690). Moderate-severe ID recorded in two patients and was formally assessed in the remaining two due to young age. However, significant DD was noted in both and in line with the diagnosis of Joubert, it can be anticipated that their presentation is within the scope of this panel.; to: Four unrelated cases reported (PMID:26477546 and 31625690). Moderate-severe ID recorded in two patients and was formally assessed in the remaining two due to young age. However, significant DD was noted in both and in line with the diagnosis of Joubert, it can be anticipated that their presentation is within the scope of this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.441 | CEP104 | Arina Puzriakova Phenotypes for gene: CEP104 were changed from JOUBERT SYNDROME to Joubert syndrome 25, 616781 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.440 | CEP104 | Arina Puzriakova Publications for gene: CEP104 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.439 | CEP104 | Arina Puzriakova Classified gene: CEP104 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.439 | CEP104 | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to support a Green rating on this panel, and so this gene will be flagged for review at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.439 | CEP104 | Arina Puzriakova Gene: cep104 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.438 | CEP104 | Arina Puzriakova Tag for-review tag was added to gene: CEP104. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.438 | CEP104 | Arina Puzriakova edited their review of gene: CEP104: Added comment: Four related cases reported (PMID:26477546 and 31625690). Moderate-severe ID recorded in two patients and was formally assessed in the remaining two due to young age. However, significant DD was noted in both and in line with the diagnosis of Joubert, it can be anticipated that their presentation is within the scope of this panel.; Changed publications: 26477546, 31625690 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.438 | CEP104 | Arina Puzriakova reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 31625690; Phenotypes: Joubert syndrome 25, 616781; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.438 | CACNA2D2 | Arina Puzriakova Classified gene: CACNA2D2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.438 | CACNA2D2 |
Arina Puzriakova Added comment: Comment on list classification: Kept rating Amber as severe GDD is a neurodegenerative manifestation that is secondary to the onset of seizures, which represent the key phenotypic feature of this disorder. This gene is Green on the Genetic epilepsy syndromes (v2.170) panel, which should be a sufficient route for detecting these cases. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.438 | CACNA2D2 | Arina Puzriakova Gene: cacna2d2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.437 | CARS2 | Arina Puzriakova Publications for gene: CARS2 were set to 25787132 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.436 | CARS2 | Arina Puzriakova Classified gene: CARS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.436 | CARS2 |
Arina Puzriakova Added comment: Comment on list classification: Kept rating Amber as developmental regression and progressive cognitive decline appear secondary to seizures, which represent the key phenotypic feature of this disorder. This gene is Green on the Inborn errors of metabolism (v2.2) panel, a component the Epilepsy super panel, which should be a sufficient route for detecting these cases. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.436 | CARS2 | Arina Puzriakova Gene: cars2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.435 | C2CD3 | Arina Puzriakova Classified gene: C2CD3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.435 | C2CD3 |
Arina Puzriakova Added comment: Comment on list classification: Despite phenotypic diversity among cases with C2CD3 variants, ID/DD is consistently reported in living patients. Therefore, this gene could be promoted from Amber to Green at the next GMS panel update (added 'for-review' tag). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.435 | C2CD3 | Arina Puzriakova Gene: c2cd3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.434 | C2CD3 | Arina Puzriakova Phenotypes for gene: C2CD3 were changed from ?Orofaciodigital syndrome XIV 615948 to Orofaciodigital syndrome XIV, 615948; Joubert-related disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.433 | C2CD3 | Arina Puzriakova Publications for gene: C2CD3 were set to 27094867; 24997988 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.432 | C2CD3 | Arina Puzriakova Tag for-review tag was added to gene: C2CD3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.432 | C2CD3 | Arina Puzriakova edited their review of gene: C2CD3: Changed publications: 24997988, 26092869, 26477546, 27094867, 30097616 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.432 | C2CD3 |
Arina Puzriakova changed review comment from: - PMID: 24997988 (2014) - Two unrelated cases with OFD syndrome and biallelic variants (p.Arg62* and p.Cys1029Gly; p.Ala1304Valfs*3, respectively) in C2CD3. In a 4-year-old male, additional manifestations included severe microcephaly (-5 SD), severe ID, micropenis, and brain malformations including Molar Tooth Sign. In the second patient, a terminated foetus, severe microcephaly (-4 SD) was combined with canonical OFD symptoms, but assessment of ID was not possible. No functional studies of the variants; however, some data supporting a role of C2CD3 in cilium assembly and function. - PMID: 26092869 (2015) - Two unrelated individuals with biallelic variants in C2CD3. Clinical details are limited but both had features of Joubert syndrome (as JBTS screening study), as well as oral features including oral frenulae and/or cleft palate. No report on ID status, but could possibly be present in view of the JBTS diagnosis. One patient also harboured biallelic variants in TTC21B. - PMID: 26477546 (2015) - Compound het variants identified in two affected sibs with a classic form of JBTS and severe GDD but without any extraneural manifestations, as described in previous cases. - PMID: 27094867 (2016) - Two sibling fetuses with skeletal dysplasia, brain malformations but no microcephaly, in association with compound het variants in C2CD3. Due to termination of pregnancies, ID status could not be established. Analysis of patient-derived fibroblasts showed impaired cilium assembly. - PMID: 30097616 (2018) - Four individuals from three unrelated families with different biallelic variants in C2CD3. Each family exhibited distinct clinical phenotypes and severity of disease: Family 1: two sibs with a diagnosis of OFD including polydactyly, cleft palate and/or incomplete cleft lip, microcephaly, brain malformations and bilateral colobomas. GDD was noted in both sibs. Family 2: fetus with occipital encephalocele and a ventricular septal defect. Similar abnormalities were identified in another sib (also a terminated fetus), but DNA analysis was not performed on the latter. Family 3: one male with various fetal anomalies, and subsequent diagnosis of JBTS following identification of consistent findings on brain MRI. Other features included DD and bilateral retina colobomas.; to: - PMID: 24997988 (2014) - Two unrelated cases with OFD syndrome and biallelic variants (p.Arg62* and p.Cys1029Gly; p.Ala1304Valfs*3, respectively) in C2CD3. In a 4-year-old male, additional manifestations included severe microcephaly (-5 SD), severe ID, micropenis, and brain malformations including Molar Tooth Sign. In the second patient, a terminated foetus, severe microcephaly (-4 SD) was combined with canonical OFD symptoms, but assessment of ID was not possible. No functional studies of the variants; however, some data supporting a role of C2CD3 in cilium assembly and function. - PMID: 26092869 (2015) - Two unrelated individuals with biallelic variants in C2CD3. Clinical details are limited but both had features of Joubert syndrome (as JBTS screening study), as well as oral features including oral frenulae and/or cleft palate. No report on ID status, but could possibly be present in view of the JBTS diagnosis. One patient also harboured biallelic variants in TTC21B. - PMID: 26477546 (2015) - Compound het variants identified in two affected sibs with a classic form of JBTS and severe GDD but without any extraneural manifestations, as described in previous cases. - PMID: 27094867 (2016) - Two sibling fetuses with skeletal dysplasia, brain malformations but no microcephaly, in association with compound het variants in C2CD3. Due to termination of pregnancies, ID status could not be established. Analysis of patient-derived fibroblasts showed impaired cilium assembly. - PMID: 30097616 (2018) - Four individuals from three unrelated families with different biallelic variants in C2CD3. Each family exhibited distinct clinical phenotypes and severity of disease: Family 1: two sibs with a diagnosis of OFD including polydactyly, cleft palate and/or incomplete cleft lip, microcephaly, brain malformations and bilateral colobomas. GDD was noted in both sibs. Family 2: fetus with encephalocele and a ventricular septal defect. Similar abnormalities were identified in a sib (also a terminated fetus), but DNA analysis was not performed on the latter. Family 3: one male with various fetal anomalies, and subsequent diagnosis of JBTS following identification of consistent findings on brain MRI. Other features included DD and bilateral retina colobomas. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.432 | C2CD3 | Arina Puzriakova reviewed gene: C2CD3: Rating: ; Mode of pathogenicity: None; Publications: 24997988, 26092869, 26477546, 27094867; Phenotypes: Orofaciodigital syndrome XIV, 615948, Joubert-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.432 | BCORL1 | Arina Puzriakova Phenotypes for gene: BCORL1 were changed from Intellectual disability, developmental delay and dysmorphism; Behavioral abnormality to Shukla-Vernon syndrome, 301029 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.431 | BCORL1 | Arina Puzriakova Publications for gene: BCORL1 were set to 24123876; 24896178; 26350204; 30941876 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.430 | BCORL1 | Arina Puzriakova Classified gene: BCORL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.430 | BCORL1 | Arina Puzriakova Added comment: Comment on list classification: Kept rating Amber in line with the previous review by Rebecca Foulger. Severe ID only exhibited by 2/4 families. No additional papers recently published. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.430 | BCORL1 | Arina Puzriakova Gene: bcorl1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.429 | MPV17 | Ivone Leong Classified gene: MPV17 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.429 | MPV17 | Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. While there are enough cases to support a gene-disease association, ID is part of a broader phenotype for this disorder. Affected individuals will more likely be assessed under mitchondrial panels. This gene is green in Mitochondrial liver disease, inborn errors of metabolism, possible mitochondrial disorder - nuclear genes and mitochondrial disorders panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.429 | MPV17 | Ivone Leong Gene: mpv17 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.428 | MPV17 | Ivone Leong Phenotypes for gene: MPV17 were changed from Gene2Phenotype confirmed gene with ID HPO to Gene2Phenotype confirmed gene with ID HPO; Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), 256810 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.427 | MPV17 | Ivone Leong Publications for gene: MPV17 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.426 | LAS1L | Ivone Leong changed review comment from: Comment on list classification: Based on the expert reviews and available evidence, this gene has been promoted from Red to Amber. As the ID severity in the second case in (PMID: 25644381) is unknown and the variant in 1 case reported by (PMID: 26358559) is predicted to be benign. Until there is further evidence this gene has been given an Amber rating.; to: Comment on list classification: Based on the expert reviews and available evidence, this gene has been promoted from Red to Amber. This gene is listed in OMIM and Gene2Phenotype with a relevant phenotype. In Gene2Phenotype it has been classified as probable course for the phenotype. As the ID severity in the second case in (PMID: 25644381) is unknown and the variant in 1 case reported by (PMID: 26358559) is predicted to be benign. Until there is further evidence this gene has been given an Amber rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.426 | LAS1L | Ivone Leong Classified gene: LAS1L as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.426 | LAS1L | Ivone Leong Added comment: Comment on list classification: Based on the expert reviews and available evidence, this gene has been promoted from Red to Amber. As the ID severity in the second case in (PMID: 25644381) is unknown and the variant in 1 case reported by (PMID: 26358559) is predicted to be benign. Until there is further evidence this gene has been given an Amber rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.426 | LAS1L | Ivone Leong Gene: las1l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.425 | LAS1L | Ivone Leong Tag watchlist tag was added to gene: LAS1L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.425 | NUP214 | Arina Puzriakova Tag for-review tag was added to gene: NUP214. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.425 | TINF2 | Arina Puzriakova Phenotypes for gene: TINF2 were changed from Dyskeratosis congenita, autosomal dominant 3 613990 to Dyskeratosis congenita, autosomal dominant 3, 613990; Revesz syndrome, 268130 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.424 | HDAC4 | Sarah Leigh Publications for gene: HDAC4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.423 | TINF2 | Arina Puzriakova Classified gene: TINF2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.423 | TINF2 |
Arina Puzriakova Added comment: Comment on list classification: Although DD can be a feature, the condition is expected to present in a syndromic manner with cytopenia, cerebellar hypoplasia and retinopathy representing key characteristics. It is expected that these indications should be sufficient for detecting cases - TINF2 is already Green on the relevant panels. Calling variants in this gene in a cohort of ID patients is therefore unlikely to be of benefit and so the rating has been kept Red. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.423 | TINF2 | Arina Puzriakova Gene: tinf2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ZMPSTE24 |
Arina Puzriakova Source Expert Review Red was added to ZMPSTE24. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ZIC3 |
Arina Puzriakova Source Expert Review Red was added to ZIC3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | XPC |
Arina Puzriakova Source Expert Review Red was added to XPC. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WRAP53 |
Arina Puzriakova Source Expert Review Red was added to WRAP53. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WNT7A |
Arina Puzriakova Source Expert Review Red was added to WNT7A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WNT3 |
Arina Puzriakova Source Expert Review Red was added to WNT3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WNT10B |
Arina Puzriakova Source Expert Review Red was added to WNT10B. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WDR35 |
Arina Puzriakova Source Expert Review Red was added to WDR35. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WDR34 |
Arina Puzriakova Source Expert Review Red was added to WDR34. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | WDR19 |
Arina Puzriakova Source Expert Review Red was added to WDR19. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | VSX2 |
Arina Puzriakova Source Expert Review Red was added to VSX2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | UVSSA |
Arina Puzriakova Source Expert Review Red was added to UVSSA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | USB1 |
Arina Puzriakova Source Expert Review Red was added to USB1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | UROS |
Arina Puzriakova Source Expert Review Red was added to UROS. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | UGT1A1 |
Arina Puzriakova Source Expert Review Red was added to UGT1A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TYRP1 |
Arina Puzriakova Source Expert Review Red was added to TYRP1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TYR |
Arina Puzriakova Source Expert Review Red was added to TYR. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TXNL4A |
Arina Puzriakova Source Expert Review Red was added to TXNL4A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TUBA8 |
Arina Puzriakova Source Expert Review Red was added to TUBA8. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TSHR |
Arina Puzriakova Source Expert Review Red was added to TSHR. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TRPV4 |
Arina Puzriakova Source Expert Review Red was added to TRPV4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TRPS1 |
Arina Puzriakova Source Expert Review Red was added to TRPS1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TRPM1 |
Arina Puzriakova Source Expert Review Red was added to TRPM1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TRIP11 |
Arina Puzriakova Source Expert Review Red was added to TRIP11. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TRAPPC2 |
Arina Puzriakova Source Expert Review Red was added to TRAPPC2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TP63 |
Arina Puzriakova Source Expert Review Red was added to TP63. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TMPRSS6 |
Arina Puzriakova Source Expert Review Red was added to TMPRSS6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TMEM126B |
Arina Puzriakova Source Expert Review Red was added to TMEM126B. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TGFB3 |
Arina Puzriakova Source Expert Review Red was added to TGFB3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TGFB2 |
Arina Puzriakova Source Expert Review Red was added to TGFB2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TEK |
Arina Puzriakova Source Expert Review Red was added to TEK. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TCF12 |
Arina Puzriakova Source Expert Review Red was added to TCF12. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBXAS1 |
Arina Puzriakova Source Expert Review Red was added to TBXAS1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBX5 |
Arina Puzriakova Source Expert Review Red was added to TBX5. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBX4 |
Arina Puzriakova Source Expert Review Red was added to TBX4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBX3 |
Arina Puzriakova Source Expert Review Red was added to TBX3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBX22 |
Arina Puzriakova Source Expert Review Red was added to TBX22. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBX20 |
Arina Puzriakova Source Expert Review Red was added to TBX20. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TBX15 |
Arina Puzriakova Source Expert Review Red was added to TBX15. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | TAB2 |
Arina Puzriakova Source Expert Review Red was added to TAB2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | STAR |
Arina Puzriakova Source Expert Review Red was added to STAR. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | SRY |
Arina Puzriakova Source Expert Review Red was added to SRY. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | SPEG |
Arina Puzriakova Source Expert Review Red was added to SPEG. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | SPAG1 |
Arina Puzriakova Source Expert Review Red was added to SPAG1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | SOX17 |
Arina Puzriakova Source Expert Review Red was added to SOX17. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | SMCHD1 |
Arina Puzriakova Source Expert Review Red was added to SMCHD1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | SCN4A |
Arina Puzriakova Source Expert Review Red was added to SCN4A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RUNX2 |
Arina Puzriakova Source Expert Review Red was added to RUNX2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RSPO4 |
Arina Puzriakova Source Expert Review Red was added to RSPO4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RSPH3 |
Arina Puzriakova Source Expert Review Red was added to RSPH3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RSPH1 |
Arina Puzriakova Source Expert Review Red was added to RSPH1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RPS19 |
Arina Puzriakova Source Expert Review Red was added to RPS19. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RPGRIP1 |
Arina Puzriakova Source Expert Review Red was added to RPGRIP1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RPE65 |
Arina Puzriakova Source Expert Review Red was added to RPE65. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ROBO3 |
Arina Puzriakova Source Expert Review Red was added to ROBO3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | RETREG1 |
Arina Puzriakova Source Expert Review Red was added to RETREG1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | PGM1 |
Arina Puzriakova Source Expert Review Red was added to PGM1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | PDE6G |
Arina Puzriakova Source Expert Review Red was added to PDE6G. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | PAX9 |
Arina Puzriakova Source Expert Review Red was added to PAX9. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | PAX3 |
Arina Puzriakova Source Expert Review Red was added to PAX3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | PAPSS2 |
Arina Puzriakova Source Expert Review Red was added to PAPSS2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | OTULIN |
Arina Puzriakova Source Expert Review Red was added to OTULIN. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | OTOGL |
Arina Puzriakova Source Expert Review Red was added to OTOGL. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ORC6 |
Arina Puzriakova Source Expert Review Red was added to ORC6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NRXN2 |
Arina Puzriakova Source Expert Review Red was added to NRXN2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NR5A1 |
Arina Puzriakova Source Expert Review Red was added to NR5A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NR2F2 |
Arina Puzriakova Source Expert Review Red was added to NR2F2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NPR2 |
Arina Puzriakova Source Expert Review Red was added to NPR2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NPHS1 |
Arina Puzriakova Source Expert Review Red was added to NPHS1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NPHP4 |
Arina Puzriakova Source Expert Review Red was added to NPHP4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NOTCH2 |
Arina Puzriakova Source Expert Review Red was added to NOTCH2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NOG |
Arina Puzriakova Source Expert Review Red was added to NOG. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NODAL |
Arina Puzriakova Source Expert Review Red was added to NODAL. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NMNAT1 |
Arina Puzriakova Source Expert Review Red was added to NMNAT1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NKX3-2 |
Arina Puzriakova Source Expert Review Red was added to NKX3-2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | NEK1 |
Arina Puzriakova Source Expert Review Red was added to NEK1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MYO5B |
Arina Puzriakova Source Expert Review Red was added to MYO5B. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MYH9 |
Arina Puzriakova Source Expert Review Red was added to MYH9. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MYH8 |
Arina Puzriakova Source Expert Review Red was added to MYH8. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MYH6 |
Arina Puzriakova Source Expert Review Red was added to MYH6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MSX2 |
Arina Puzriakova Source Expert Review Red was added to MSX2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MSX1 |
Arina Puzriakova Source Expert Review Red was added to MSX1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MNX1 |
Arina Puzriakova Source Expert Review Red was added to MNX1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MMP13 |
Arina Puzriakova Source Expert Review Red was added to MMP13. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MFRP |
Arina Puzriakova Source Expert Review Red was added to MFRP. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MESP2 |
Arina Puzriakova Source Expert Review Red was added to MESP2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MC2R |
Arina Puzriakova Source Expert Review Red was added to MC2R. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MATN3 |
Arina Puzriakova Source Expert Review Red was added to MATN3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | MAP3K1 |
Arina Puzriakova Source Expert Review Red was added to MAP3K1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LTBP3 |
Arina Puzriakova Source Expert Review Red was added to LTBP3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LTBP2 |
Arina Puzriakova Source Expert Review Red was added to LTBP2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LRRC6 |
Arina Puzriakova Source Expert Review Red was added to LRRC6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LRP4 |
Arina Puzriakova Source Expert Review Red was added to LRP4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LMX1B |
Arina Puzriakova Source Expert Review Red was added to LMX1B. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LMNA |
Arina Puzriakova Source Expert Review Red was added to LMNA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LHX4 |
Arina Puzriakova Source Expert Review Red was added to LHX4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LHX3 |
Arina Puzriakova Source Expert Review Red was added to LHX3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LFNG |
Arina Puzriakova Source Expert Review Red was added to LFNG. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LEMD3 |
Arina Puzriakova Source Expert Review Red was added to LEMD3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | LDB3 |
Arina Puzriakova Source Expert Review Red was added to LDB3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KLHL40 |
Arina Puzriakova Source Expert Review Red was added to KLHL40. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KLF1 |
Arina Puzriakova Source Expert Review Red was added to KLF1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KIT |
Arina Puzriakova Source Expert Review Red was added to KIT. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KIRREL3 |
Arina Puzriakova Source Expert Review Red was added to KIRREL3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KIF22 |
Arina Puzriakova Source Expert Review Red was added to KIF22. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KCTD1 |
Arina Puzriakova Source Expert Review Red was added to KCTD1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KCNQ1 |
Arina Puzriakova Source Expert Review Red was added to KCNQ1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KCND3 |
Arina Puzriakova Source Expert Review Red was added to KCND3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | KBTBD13 |
Arina Puzriakova Source Expert Review Red was added to KBTBD13. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | JAK3 |
Arina Puzriakova Source Expert Review Red was added to JAK3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | JAGN1 |
Arina Puzriakova Source Expert Review Red was added to JAGN1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | JAG1 |
Arina Puzriakova Source Expert Review Red was added to JAG1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IRF6 |
Arina Puzriakova Source Expert Review Red was added to IRF6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | INPPL1 |
Arina Puzriakova Source Expert Review Red was added to INPPL1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IMPAD1 |
Arina Puzriakova Source Expert Review Red was added to IMPAD1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IL11RA |
Arina Puzriakova Source Expert Review Red was added to IL11RA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IHH |
Arina Puzriakova Source Expert Review Red was added to IHH. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IGF2 |
Arina Puzriakova Source Expert Review Red was added to IGF2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IFT80 |
Arina Puzriakova Source Expert Review Red was added to IFT80. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IFT122 |
Arina Puzriakova Source Expert Review Red was added to IFT122. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | IFITM5 |
Arina Puzriakova Source Expert Review Red was added to IFITM5. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HYDIN |
Arina Puzriakova Source Expert Review Red was added to HYDIN. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HYAL1 |
Arina Puzriakova Source Expert Review Red was added to HYAL1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HSF4 |
Arina Puzriakova Source Expert Review Red was added to HSF4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HSD3B7 |
Arina Puzriakova Source Expert Review Red was added to HSD3B7. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HR |
Arina Puzriakova Source Expert Review Red was added to HR. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HPSE2 |
Arina Puzriakova Source Expert Review Red was added to HPSE2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HPS1 |
Arina Puzriakova Source Expert Review Red was added to HPS1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HPGD |
Arina Puzriakova Source Expert Review Red was added to HPGD. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HOXD13 |
Arina Puzriakova Source Expert Review Red was added to HOXD13. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HOXC13 |
Arina Puzriakova Source Expert Review Red was added to HOXC13. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HOXA13 |
Arina Puzriakova Source Expert Review Red was added to HOXA13. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HNF4A |
Arina Puzriakova Source Expert Review Red was added to HNF4A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | HMGCS2 |
Arina Puzriakova Source Expert Review Red was added to HMGCS2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GUCY2C |
Arina Puzriakova Source Expert Review Red was added to GUCY2C. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GRM6 |
Arina Puzriakova Source Expert Review Red was added to GRM6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GRHL3 |
Arina Puzriakova Source Expert Review Red was added to GRHL3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GPR179 |
Arina Puzriakova Source Expert Review Red was added to GPR179. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GNAI3 |
Arina Puzriakova Source Expert Review Red was added to GNAI3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GLMN |
Arina Puzriakova Source Expert Review Red was added to GLMN. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GLE1 |
Arina Puzriakova Source Expert Review Red was added to GLE1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GJA8 |
Arina Puzriakova Source Expert Review Red was added to GJA8. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GJA3 |
Arina Puzriakova Source Expert Review Red was added to GJA3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GJA1 |
Arina Puzriakova Source Expert Review Red was added to GJA1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GHR |
Arina Puzriakova Source Expert Review Red was added to GHR. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GDF6 |
Arina Puzriakova Source Expert Review Red was added to GDF6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GDF5 |
Arina Puzriakova Source Expert Review Red was added to GDF5. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GATA4 |
Arina Puzriakova Source Expert Review Red was added to GATA4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GATA2 |
Arina Puzriakova Source Expert Review Red was added to GATA2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GAS8 |
Arina Puzriakova Source Expert Review Red was added to GAS8. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GALK1 |
Arina Puzriakova Source Expert Review Red was added to GALK1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | GAA |
Arina Puzriakova Source Expert Review Red was added to GAA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FZD6 |
Arina Puzriakova Source Expert Review Red was added to FZD6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FYCO1 |
Arina Puzriakova Source Expert Review Red was added to FYCO1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FXN |
Arina Puzriakova Source Expert Review Red was added to FXN. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FTL |
Arina Puzriakova Source Expert Review Red was added to FTL. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FOXN1 |
Arina Puzriakova Source Expert Review Red was added to FOXN1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FOXF1 |
Arina Puzriakova Source Expert Review Red was added to FOXF1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FOXE3 |
Arina Puzriakova Source Expert Review Red was added to FOXE3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FOXE1 |
Arina Puzriakova Source Expert Review Red was added to FOXE1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FOXC2 |
Arina Puzriakova Source Expert Review Red was added to FOXC2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FOXC1 |
Arina Puzriakova Source Expert Review Red was added to FOXC1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FLT4 |
Arina Puzriakova Source Expert Review Red was added to FLT4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FLNB |
Arina Puzriakova Source Expert Review Red was added to FLNB. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FKBP14 |
Arina Puzriakova Source Expert Review Red was added to FKBP14. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FHL1 |
Arina Puzriakova Source Expert Review Red was added to FHL1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FGF3 |
Arina Puzriakova Source Expert Review Red was added to FGF3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FGF10 |
Arina Puzriakova Source Expert Review Red was added to FGF10. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FBXW4 |
Arina Puzriakova Source Expert Review Red was added to FBXW4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FBP1 |
Arina Puzriakova Source Expert Review Red was added to FBP1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FBN1 |
Arina Puzriakova Source Expert Review Red was added to FBN1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FAM20A |
Arina Puzriakova Source Expert Review Red was added to FAM20A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | FAM161A |
Arina Puzriakova Source Expert Review Red was added to FAM161A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | EYA1 |
Arina Puzriakova Source Expert Review Red was added to EYA1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | EVC2 |
Arina Puzriakova Source Expert Review Red was added to EVC2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | EVC |
Arina Puzriakova Source Expert Review Red was added to EVC. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ERF |
Arina Puzriakova Source Expert Review Red was added to ERF. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ERCC4 |
Arina Puzriakova Source Expert Review Red was added to ERCC4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | EOGT |
Arina Puzriakova Source Expert Review Red was added to EOGT. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ENPP1 |
Arina Puzriakova Source Expert Review Red was added to ENPP1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | EDNRA |
Arina Puzriakova Source Expert Review Red was added to EDNRA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | EDA |
Arina Puzriakova Source Expert Review Red was added to EDA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ECEL1 |
Arina Puzriakova Source Expert Review Red was added to ECEL1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DYNC2H1 |
Arina Puzriakova Source Expert Review Red was added to DYNC2H1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DVL1 |
Arina Puzriakova Source Expert Review Red was added to DVL1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DSTYK |
Arina Puzriakova Source Expert Review Red was added to DSTYK. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DSPP |
Arina Puzriakova Source Expert Review Red was added to DSPP. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DNAAF4 |
Arina Puzriakova Source Expert Review Red was added to DNAAF4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DNAAF3 |
Arina Puzriakova Source Expert Review Red was added to DNAAF3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DMP1 |
Arina Puzriakova Source Expert Review Red was added to DMP1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DLL4 |
Arina Puzriakova Source Expert Review Red was added to DLL4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DLL3 |
Arina Puzriakova Source Expert Review Red was added to DLL3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DDB2 |
Arina Puzriakova Source Expert Review Red was added to DDB2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | DCC |
Arina Puzriakova Source Expert Review Red was added to DCC. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CYP1B1 |
Arina Puzriakova Source Expert Review Red was added to CYP1B1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CTSK |
Arina Puzriakova Source Expert Review Red was added to CTSK. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CTSF |
Arina Puzriakova Source Expert Review Red was added to CTSF. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CTNS |
Arina Puzriakova Source Expert Review Red was added to CTNS. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRYGD |
Arina Puzriakova Source Expert Review Red was added to CRYGD. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRYBB3 |
Arina Puzriakova Source Expert Review Red was added to CRYBB3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRYBB2 |
Arina Puzriakova Source Expert Review Red was added to CRYBB2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRYBB1 |
Arina Puzriakova Source Expert Review Red was added to CRYBB1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRYBA1 |
Arina Puzriakova Source Expert Review Red was added to CRYBA1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRYAA |
Arina Puzriakova Source Expert Review Red was added to CRYAA. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRX |
Arina Puzriakova Source Expert Review Red was added to CRX. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CRB1 |
Arina Puzriakova Source Expert Review Red was added to CRB1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COMP |
Arina Puzriakova Source Expert Review Red was added to COMP. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL9A3 |
Arina Puzriakova Source Expert Review Red was added to COL9A3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL9A2 |
Arina Puzriakova Source Expert Review Red was added to COL9A2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL9A1 |
Arina Puzriakova Source Expert Review Red was added to COL9A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL6A1 |
Arina Puzriakova Source Expert Review Red was added to COL6A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL4A4 |
Arina Puzriakova Source Expert Review Red was added to COL4A4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL4A3 |
Arina Puzriakova Source Expert Review Red was added to COL4A3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL2A1 |
Arina Puzriakova Source Expert Review Red was added to COL2A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL1A1 |
Arina Puzriakova Source Expert Review Red was added to COL1A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL18A1 |
Arina Puzriakova Source Expert Review Red was added to COL18A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL11A1 |
Arina Puzriakova Source Expert Review Red was added to COL11A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | COL10A1 |
Arina Puzriakova Source Expert Review Red was added to COL10A1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CLDN19 |
Arina Puzriakova Source Expert Review Red was added to CLDN19. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CLCN7 |
Arina Puzriakova Source Expert Review Red was added to CLCN7. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CIB2 |
Arina Puzriakova Source Expert Review Red was added to CIB2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CHUK |
Arina Puzriakova Source Expert Review Red was added to CHUK. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CHSY1 |
Arina Puzriakova Source Expert Review Red was added to CHSY1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CHST3 |
Arina Puzriakova Source Expert Review Red was added to CHST3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CHRNG |
Arina Puzriakova Source Expert Review Red was added to CHRNG. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CHRDL1 |
Arina Puzriakova Source Expert Review Red was added to CHRDL1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CHM |
Arina Puzriakova Source Expert Review Red was added to CHM. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CDH3 |
Arina Puzriakova Source Expert Review Red was added to CDH3. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CDH23 |
Arina Puzriakova Source Expert Review Red was added to CDH23. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CCT5 |
Arina Puzriakova Source Expert Review Red was added to CCT5. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CCNO |
Arina Puzriakova Source Expert Review Red was added to CCNO. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CCDC65 |
Arina Puzriakova Source Expert Review Red was added to CCDC65. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CCDC40 |
Arina Puzriakova Source Expert Review Red was added to CCDC40. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CCDC114 |
Arina Puzriakova Source Expert Review Red was added to CCDC114. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | CCDC103 |
Arina Puzriakova Source Expert Review Red was added to CCDC103. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | C4orf26 |
Arina Puzriakova Source Expert Review Red was added to C4orf26. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | C2orf71 |
Arina Puzriakova Source Expert Review Red was added to C2orf71. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | C19orf12 |
Arina Puzriakova Source Expert Review Red was added to C19orf12. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | BMPR1B |
Arina Puzriakova Source Expert Review Red was added to BMPR1B. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | BMPER |
Arina Puzriakova Source Expert Review Red was added to BMPER. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | BICD2 |
Arina Puzriakova Source Expert Review Red was added to BICD2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | BHLHA9 |
Arina Puzriakova Source Expert Review Red was added to BHLHA9. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | BGN |
Arina Puzriakova Source Expert Review Red was added to BGN. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | BFSP2 |
Arina Puzriakova Source Expert Review Red was added to BFSP2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ATP6V1B1 |
Arina Puzriakova Source Expert Review Red was added to ATP6V1B1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.421 | ARHGEF6 |
Arina Puzriakova Source Expert Review Red was added to ARHGEF6. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | ITFG2 |
Konstantinos Varvagiannis gene: ITFG2 was added gene: ITFG2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z Phenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia Penetrance for gene: ITFG2 were set to Complete Review for gene: ITFG2 was set to AMBER Added comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51). Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS. Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)]. As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306). Please consider inclusion in the ID panel with amber rating, pending further details. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | USP7 | Konstantinos Varvagiannis edited their review of gene: USP7: Changed publications: 26365382, 19946331, 33012787 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | USP7 | Konstantinos Varvagiannis changed review comment from: Please consider also PMID : 33012787 for Green rating (several cases reported).; to: Please consider also PMID : 33012787 for Green rating (several cases reported to date). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | USP7 | Konstantinos Varvagiannis commented on gene: USP7: Please consider also PMID : 33012787 for Green rating (several cases reported). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | SHMT2 |
Konstantinos Varvagiannis gene: SHMT2 was added gene: SHMT2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHMT2 were set to 33015733 Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly Penetrance for gene: SHMT2 were set to Complete Review for gene: SHMT2 was set to GREEN Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants. All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs. Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF. Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes. While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction. Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect. The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). Overall this gene can be considered for inclusion with (probably) green rating in gene panels for ID, metabolic / mitochondrial disorders, cardiomyopathy, congenital microcephaly, corpus callosum anomalies, etc. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | ABCB11 | Arina Puzriakova Classified gene: ABCB11 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | ABCB11 | Arina Puzriakova Added comment: Comment on list classification: Downgraded from Amber to Red in context of the review by Konstantinos Varvagiannis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.420 | ABCB11 | Arina Puzriakova Gene: abcb11 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.419 | ACAN | Arina Puzriakova Classified gene: ACAN as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.419 | ACAN | Arina Puzriakova Added comment: Comment on list classification: Downgraded from Amber to Red in context of the review by Konstantinos Varvagiannis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.419 | ACAN | Arina Puzriakova Gene: acan has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.418 | ATP8B1 | Arina Puzriakova Classified gene: ATP8B1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.418 | ATP8B1 | Arina Puzriakova Gene: atp8b1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.417 | ATP8B1 | Arina Puzriakova changed review comment from: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark; to: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Konstantinos Varvagiannis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.417 | KAT5 | Arina Puzriakova Phenotypes for gene: KAT5 were changed from to Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.416 | KAT5 | Arina Puzriakova Publications for gene: KAT5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.415 | KAT5 | Arina Puzriakova Mode of inheritance for gene: KAT5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.415 | KAT5 | Arina Puzriakova Mode of inheritance for gene: KAT5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.414 | KAT5 | Arina Puzriakova Classified gene: KAT5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.414 | KAT5 | Arina Puzriakova Added comment: Comment on list classification: Rating upgraded from Red to Amber. There is a sufficient number of unrelated cases reported in PMID:32822602 to promoted this gene to Green at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.414 | KAT5 | Arina Puzriakova Gene: kat5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.413 | KAT5 | Arina Puzriakova Tag for-review tag was added to gene: KAT5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.413 | SCAF4 | Arina Puzriakova Phenotypes for gene: SCAF4 were changed from to SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.412 | SCAF4 | Arina Puzriakova Classified gene: SCAF4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.412 | SCAF4 |
Arina Puzriakova Added comment: Comment on list classification: At least 8 unrelated individuals reported in PMID:32730804 with a neurodevelopmental disorder characterised by DD/ID, mostly in the mild range (severe in only one individual). Rating Amber in view of the mild ID presentation. This may be reviewed if further cases are reported with more severe manifestations of relevant phenotypes. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.412 | SCAF4 | Arina Puzriakova Gene: scaf4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.411 | SCAF4 | Arina Puzriakova commented on gene: SCAF4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.411 | SCAF4 | Arina Puzriakova Publications for gene: SCAF4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.410 | NEDD4L |
Eleanor Williams changed review comment from: Associated with Periventricular nodular heterotopia 7 #617201 (AD) in OMIM. PMID: 27694961 - Broix et al 2016 - report 4 different de novo missense changes in NEDD4L in a total of five unrelated patients with periventricular nodular heterotopia and neurodevelopmental delay, and in a additional familial case with a similar phenotype and a previously found missense variant. In the familial case, two affected siblings were found to be heterozygous for the variant, the father and an unaffected sibling did not carry the variant, and the mother was found to show somatic mosaicism of NEDD4L variant. Functional studies showed a sensitivity of PNH-associated mutants to proteasome degradation.; to: Associated with Periventricular nodular heterotopia 7 #617201 (AD) in OMIM. PMID: 27694961 - Broix et al 2016 - report 4 different de novo missense changes in NEDD4L in a total of five unrelated patients with periventricular nodular heterotopia and neurodevelopmental delay, and in a additional familial case with a similar phenotype and a previously found missense variant. In the familial case, two affected siblings were found to be heterozygous for the variant, the father and an unaffected sibling did not carry the variant, and the mother was found to show somatic mosaicism of NEDD4L variant. Functional studies showed a sensitivity of PNH-associated mutants to proteasome degradation. Seizures were reported in some but not all affected individuals. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.410 | NEDD4L | Eleanor Williams Tag for-review tag was added to gene: NEDD4L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.410 | NEDD4L | Eleanor Williams Classified gene: NEDD4L as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.410 | NEDD4L | Eleanor Williams Gene: nedd4l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.409 | NEDD4L | Eleanor Williams Classified gene: NEDD4L as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.409 | NEDD4L | Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber, but there are sufficient cases with a severe developmental delay phenotype for it to be rated green. It should therefore be reviewed at the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.409 | NEDD4L | Eleanor Williams Gene: nedd4l has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.408 | NEDD4L | Eleanor Williams Phenotypes for gene: NEDD4L were changed from EPILEPTIC ENCEPHALOPATHY to Periventricular nodular heterotopia 7, 617201 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.408 | NEDD4L | Eleanor Williams Publications for gene: NEDD4L were set to 23934111 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.407 | NEDD4L | Eleanor Williams reviewed gene: NEDD4L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27694961; Phenotypes: Periventricular nodular heterotopia 7, 617201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.407 | NUP214 | Eleanor Williams Publications for gene: NUP214 were set to 31178128 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.406 | NUP214 | Eleanor Williams Classified gene: NUP214 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.406 | NUP214 |
Eleanor Williams Added comment: Comment on list classification: Promoting this gene from Grey to Amber. Several cases reported, but developmental delay not reported in some cases until after febrile events. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.406 | NUP214 | Eleanor Williams Gene: nup214 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.405 | NUP214 |
Eleanor Williams changed review comment from: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable). PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected siblings in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls, PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death. Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G. PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls. ; to: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable). PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected siblings in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls, PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death (<2 year old). Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G. PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.405 | NUP214 |
Eleanor Williams changed review comment from: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable). PMID: 31178128 - Fichtman et al 2019 - report on two families. Family A have first-cousin parents of Palestinian descent. The proband exhibited minor developmental delay from infancy, presented with ataxia, mental retardation, and intractable epilepsy and died at 11 years. He suffered deterioration in association with febrile illnesses. His cousin presented at 5.5 months with partially reversible encephalopathy and developmental regression after a febrile illness. Family B were sisters born to non-consanguineous parents of Northern European (non-Finnish) descent. The older sister had nystagmus at 2 months and mild hypotonia, but she was otherwise meeting milestones appropriately . At 15 months of age, she developed a fever that led to a rapid neurological decline, seizures, and abnormal movements. The younger sister presented at 7 months with failure to thrive and hyponatremia but was meeting developmental milestones appropriately. By 24 months of age, she had motor and speech delay, ataxic gait, and occasional very mild head bobbing. In family A a homozygous NUP214 p.Arg38Cys variant segregated with the disease in available family members. In family B the sisters were found to be compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6).; to: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable). PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected siblings in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls, PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death. Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G. PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.405 | NUP214 | Eleanor Williams Phenotypes for gene: NUP214 were changed from developmental delay; intellectual disability; epileptic encephalopathy; developmental regression; microcephaly to developmental delay; intellectual disability; epileptic encephalopathy; developmental regression; microcephaly; {Encephalopathy, acute, infection-induced, susceptibility to, 9}, 618426 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.404 | NUP214 | Eleanor Williams reviewed gene: NUP214: Rating: AMBER; Mode of pathogenicity: None; Publications: 31178128; Phenotypes: {Encephalopathy, acute, infection-induced, susceptibility to, 9}, 618426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.404 | GPSM2 | Eleanor Williams edited their review of gene: GPSM2: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.404 | GPSM2 | Eleanor Williams Classified gene: GPSM2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.404 | GPSM2 | Eleanor Williams Added comment: Comment on list classification: Leaving this gene as green just now, but as there are only 2 families out of 19 in which mild cognitive delay is seen then the recommendation would be to rate this gene amber. This gene should be reviewed at the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.404 | GPSM2 | Eleanor Williams Gene: gpsm2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.403 | GPSM2 | Eleanor Williams Tag for-review tag was added to gene: GPSM2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.403 | GPSM2 | Eleanor Williams Phenotypes for gene: GPSM2 were changed from DEAFNESS AUTOSOMAL RECESSIVE TYPE 82 to Chudley-McCullough syndrome, 604213 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.402 | GPSM2 | Eleanor Williams Publications for gene: GPSM2 were set to 22578326 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.401 | GPSM2 |
Eleanor Williams changed review comment from: Associated with Chudley-McCullough syndrome604213 in OMIM Summary: From 19 reported families, 3 individuals from 2 families showed cognitive delay. PMID: 27180139 - Hemzeh et al 2016 - report two brothers from a Yemeni family who were diagnosed clinically with CMS then tested for GPSM2 mutations using Sanger sequencing. A homozygous mutation in GPSM2 was found in both brothers (c.1055C > A) leading to a truncating protein change; (p.Ser352*). The 12 year old brother showed cognitive delay, noted by the inability to tell the time in minutes, or to follow complex commands. The 11 year old brother could speak in sentences but with poor articulation, and could not respond to complex commands. PMID: 23494849 - Almomani et al 2013 - report three patients from two unrelated Dutch families with CMS were investigated in which the same c.1473delG variant observed in 4 of the Menonite families by Doherty et al was observed. All three patients had normal cognitive abilities. PMID: 22578326 - Doherty et al 2012 - report on 5 Menonite, 1 European-American, 1 Dutch and 1 Mexican-American family in which probands had severe/profound hearing loss and ventriculomegaly (total of 12 affected individuals). They also look again at the patients reported with autosomal recessive nonsyndromic deafness (DFNB82) by Walsh et al 2010 (PMID: 20602914, 1 proband ina Pakistani family) and Yariz et al 2012 (PMID: 21348867, 3 probands in a Turkish family) who they found had brain abnormalities consistent with with a diagnosis of Chudley-McCullough syndrome. Oout of the 16 patients reported, only one had developmental issues beyond what is typically seen in individuals with severe hearing loss. - -; to: Associated with Chudley-McCullough syndrome604213 in OMIM Summary: From 19 reported families, 3 individuals from 2 families showed cognitive delay. PMID: 27180139 - Hemzeh et al 2016 - report two brothers from a Yemeni family who were diagnosed clinically with CMS then tested for GPSM2 mutations using Sanger sequencing. A homozygous mutation in GPSM2 was found in both brothers (c.1055C > A) leading to a truncating protein change; (p.Ser352*). The 12 year old brother showed cognitive delay, noted by the inability to tell the time in minutes, or to follow complex commands. The 11 year old brother could speak in sentences but with poor articulation, and could not respond to complex commands. The poor articulation was thought to be due to late cochlear implant surgery. PMID: 23494849 - Almomani et al 2013 - report three patients from two unrelated Dutch families with CMS were investigated in which the same c.1473delG variant observed in 4 of the Menonite families by Doherty et al was observed. All three patients had normal cognitive abilities. PMID: 22578326 - Doherty et al 2012 - report on 5 Menonite, 1 European-American, 1 Dutch and 1 Mexican-American family in which probands had severe/profound hearing loss and ventriculomegaly (total of 12 affected individuals). They also look again at the patients reported with autosomal recessive nonsyndromic deafness (DFNB82) by Walsh et al 2010 (PMID: 20602914, 1 proband ina Pakistani family) and Yariz et al 2012 (PMID: 21348867, 3 probands in a Turkish family) who they found had brain abnormalities consistent with with a diagnosis of Chudley-McCullough syndrome. Oout of the 16 patients reported, only one had developmental issues beyond what is typically seen in individuals with severe hearing loss. - - |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.401 | GPSM2 | Eleanor Williams edited their review of gene: GPSM2: Changed publications: 27180139, 23494849, 22578326, 20602914, 21348867; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.401 | GPSM2 | Eleanor Williams commented on gene: GPSM2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.401 | USP18 | Arina Puzriakova Classified gene: USP18 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.401 | USP18 |
Arina Puzriakova Added comment: Comment on list classification: DD reported in one surviving patient. However, this only became apparent following treatment which was administered after genetic diagnosis was already achieved. DD is therefore unlikely represent the clinical indication to prompt testing in the neonatal period. Therefore keeping rating Red on the ID panel. USP18 is Green on other relevant panels (White matter disorders and cerebral calcification, PID) which should be adequate for detecting these cases. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.401 | USP18 | Arina Puzriakova Gene: usp18 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.400 | USP18 | Arina Puzriakova commented on gene: USP18: Added 'treatable' tag as clinical remission was achieved in a patient following rapid genetic diagnosis and subsequent treatment with the JAK inhibitor ruxolitinib | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.400 | FLVCR1 | Eleanor Williams Tag for-review tag was added to gene: FLVCR1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.400 | USP18 | Arina Puzriakova Tag treatable tag was added to gene: USP18. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.400 | FLVCR1 | Eleanor Williams Classified gene: FLVCR1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.400 | FLVCR1 | Eleanor Williams Added comment: Comment on list classification: Leaving this gene green for now, but only one case where intellectual disability was reported. This gene should be updated at the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.400 | FLVCR1 | Eleanor Williams Gene: flvcr1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.399 | USP18 | Arina Puzriakova Publications for gene: USP18 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.398 | USP18 | Arina Puzriakova Mode of inheritance for gene: USP18 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.397 | FLVCR1 | Eleanor Williams edited their review of gene: FLVCR1: Changed rating: RED; Changed publications: 30656474, 22279524, 21267618, 21070897, 9409377, 30444160; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.397 | USP18 | Arina Puzriakova reviewed gene: USP18: Rating: ; Mode of pathogenicity: None; Publications: 12833411, 27325888, 31940699; Phenotypes: Pseudo-TORCH syndrome 2, 617397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.397 | B9D1 | Ivone Leong Classified gene: B9D1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.397 | B9D1 | Ivone Leong Added comment: Comment on list classification: This gene has been promoted from Red to Amber. Mild ID was only seen in 1 case. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.397 | B9D1 | Ivone Leong Gene: b9d1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.396 | MGP | Sarah Leigh Publications for gene: MGP were set to 15810001; 9916809 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.395 | HYLS1 | Catherine Snow Tag for-review tag was added to gene: HYLS1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.395 | HYLS1 | Catherine Snow reviewed gene: HYLS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrolethalus syndrome, MIM#236680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.395 | MGP | Sarah Leigh Tag for-review tag was added to gene: MGP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.395 | MGP | Sarah Leigh reviewed gene: MGP: Rating: RED; Mode of pathogenicity: None; Publications: 24458983, 29928182, 25123378, 26349188, 26758921; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.395 | B9D1 | Ivone Leong Publications for gene: B9D1 were set to 24886560; 25920555 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.394 | FLVCR1 | Eleanor Williams commented on gene: FLVCR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.394 | MGP | Sarah Leigh Phenotypes for gene: MGP were changed from KEUTEL SYNDROME to Keutel syndrome 245150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.393 | MADD | Ivone Leong Tag for-review tag was added to gene: MADD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.393 | LGI4 | Sarah Leigh reviewed gene: LGI4: Rating: RED; Mode of pathogenicity: None; Publications: 28318499; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.393 | MADD | Ivone Leong Classified gene: MADD as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.393 | MADD | Ivone Leong Added comment: Comment on list classification: Based on expert review provided by Konstantinos Varvagiannis and Zornitza Stark, there is enough evidence to support a gene-disease association. This gene has been promoted from Red to Amber and will be promoted to Green status at next panel review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.393 | MADD | Ivone Leong Gene: madd has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.392 | MADD | Ivone Leong Publications for gene: MADD were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.391 | MADD | Ivone Leong Phenotypes for gene: MADD were changed from to Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, 619005; DEEAH syndrome, 619004 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.390 | USP18 | Arina Puzriakova Phenotypes for gene: USP18 were changed from to Pseudo-TORCH syndrome 2, 617397 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.389 | DLL1 | Catherine Snow Publications for gene: DLL1 were set to 31353024 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.388 | LGI4 | Sarah Leigh Tag for-review tag was added to gene: LGI4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.388 | DLL1 | Catherine Snow Classified gene: DLL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.388 | DLL1 | Catherine Snow Added comment: Comment on list classification: Comment on list classification: There is a sufficient number of cases to rate this gene Green at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.388 | DLL1 | Catherine Snow Gene: dll1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.387 | DLL1 | Catherine Snow Tag for-review tag was added to gene: DLL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.387 | DLL1 | Catherine Snow edited their review of gene: DLL1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.387 | DLL1 | Catherine Snow reviewed gene: DLL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31353024, 31602192; Phenotypes: Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures 618709; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.387 | TBR1 | Ivone Leong Publications for gene: TBR1 were set to 23160955 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.386 | TBR1 | Ivone Leong Phenotypes for gene: TBR1 were changed from AUTISM to Autism; Intellectual developmental disorder with autism and speech delay, 606053; Abnormal cortical gyration | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.385 | RHEB | Arina Puzriakova Classified gene: RHEB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.385 | RHEB | Arina Puzriakova Added comment: Comment on list classification: Three individuals from two unrelated families reported in PMID:29051493 with severe-profound ID - sufficient evidence to rate this gene Amber (previously erroneously demoted to Red). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.385 | RHEB | Arina Puzriakova Gene: rheb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.384 | CTNND1 | Eleanor Williams Classified gene: CTNND1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.384 | CTNND1 | Eleanor Williams Added comment: Comment on list classification: Rating as amber but could potentially be green. Individuals from 5/9 families have reported developmental delay/learning difficulty. This gene should be reviewed at the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.384 | CTNND1 | Eleanor Williams Gene: ctnnd1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.383 | CTNND1 | Eleanor Williams Tag for-review tag was added to gene: CTNND1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.383 | CTNND1 | Eleanor Williams Phenotypes for gene: CTNND1 were changed from to developmental delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.382 | CTNND1 |
Eleanor Williams gene: CTNND1 was added gene: CTNND1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CTNND1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CTNND1 were set to 32196547 Review for gene: CTNND1 was set to GREEN Added comment: PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.381 | WDR83OS |
Ivone Leong gene: WDR83OS was added gene: WDR83OS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WDR83OS were set to 30250217 Phenotypes for gene: WDR83OS were set to Intellectual disability Review for gene: WDR83OS was set to RED Added comment: One consanguineous family with three affected individuals with homozygous split site variant in this gene. All three have ID. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.380 | YIF1B |
Arina Puzriakova changed review comment from: Comment on list classification: There is a sufficient number of cases to rate this gene Green at the next GMS panel update. GDD was reported in all 6 patients (5 families). At ages 4-11yrs, the best achieved social and language skills were limited to sounds in 4 individuals, and partial babbling or vocalisation in the remaining two, respectively.; to: Comment on list classification: There is a sufficient number of cases to rate this gene Green at the next GMS panel update. - PMID: 32006098: GDD was reported in all 6 patients (5 families). At ages 4-11yrs, the best achieved social and language skills were limited to sounds in 4 individuals, and partial babbling or vocalisation in the remaining two, respectively. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.380 | YIF1B |
Arina Puzriakova changed review comment from: Comment on list classification: There are a sufficient number of cases to rate this gene Green at the next GMS panel update. GDD was reported in all 6 patients (5 families). At ages 4-11yrs, the best achieved social and language skills were limited to sounds in 4 individuals, and partial babbling or vocalisation in the remaining two, respectively.; to: Comment on list classification: There is a sufficient number of cases to rate this gene Green at the next GMS panel update. GDD was reported in all 6 patients (5 families). At ages 4-11yrs, the best achieved social and language skills were limited to sounds in 4 individuals, and partial babbling or vocalisation in the remaining two, respectively. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.380 | YIF1B | Arina Puzriakova Classified gene: YIF1B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.380 | YIF1B |
Arina Puzriakova Added comment: Comment on list classification: There are a sufficient number of cases to rate this gene Green at the next GMS panel update. GDD was reported in all 6 patients (5 families). At ages 4-11yrs, the best achieved social and language skills were limited to sounds in 4 individuals, and partial babbling or vocalisation in the remaining two, respectively. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.380 | YIF1B | Arina Puzriakova Gene: yif1b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.379 | YIF1B | Arina Puzriakova Tag for-review tag was added to gene: YIF1B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.379 | UGDH | Arina Puzriakova Classified gene: UGDH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.379 | UGDH |
Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update. Multiple patients from over 20 unrelated families, all with moderate-to-severe ID in association with biallelic variants in UGDH. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.379 | UGDH | Arina Puzriakova Gene: ugdh has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.378 | UGDH | Arina Puzriakova Tag for-review tag was added to gene: UGDH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.378 | SPTBN4 | Arina Puzriakova Classified gene: SPTBN4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.378 | SPTBN4 |
Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update. Severe-to-profound DD and/or ID reported in all but one family with a milder phenotype (at least 9 total families described with different biallelic variants in SPTBN4). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.378 | SPTBN4 | Arina Puzriakova Gene: sptbn4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.377 | SPTBN4 | Arina Puzriakova Tag for-review tag was added to gene: SPTBN4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.377 | NR4A2 | Arina Puzriakova Classified gene: NR4A2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.377 | NR4A2 |
Arina Puzriakova Added comment: Comment on list classification: This gene will be flagged for review at the date of next GMS panel update (added 'for-review' tag). The recent paper flagged by Konstantinos Varvagiannis (PMID:32366965) includes 2 unrelated patients with severe ID and 2 with moderate-severe ID. This is within the scope of the panel and the number of cases now reach threshold for inclusion with a Green rating. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.377 | NR4A2 | Arina Puzriakova Gene: nr4a2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.376 | NR4A2 | Arina Puzriakova Tag for-review tag was added to gene: NR4A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.376 | NR4A2 | Arina Puzriakova Publications for gene: NR4A2 were set to 29770430; 30504930; 28544326; 27569545; 23554088; 28135719; 27479843; 25363768; https://doi.org/10.1101/516625 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.375 | TNRC6B | Arina Puzriakova Tag for-review tag was added to gene: TNRC6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.375 | TNRC6B | Arina Puzriakova Classified gene: TNRC6B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.375 | TNRC6B |
Arina Puzriakova Added comment: Comment on list classification: This is a borderline Amber/Green gene, and should be reviewed at the date of next GMS panel update (added 'for-review' tag). Phenotype is primarily characterised by neurobehavioral abnormalities, including DD (particularly speech impairment) in all cases, as well as variable features of autism, ADHD, impulsivity, anger and aggressiveness. Cognitive abilities were varied, and a formal diagnosis of ID was only attained in 4 patients. Nonetheless, this likely represents the most appropriate panel for capturing these cases and therefore a Green rating should be considered. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.375 | TNRC6B | Arina Puzriakova Gene: tnrc6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.374 | TNRC6B | Arina Puzriakova Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behaviour | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.373 | TNRC6B | Arina Puzriakova Publications for gene: TNRC6B were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.372 | TNRC6B | Arina Puzriakova Mode of inheritance for gene: TNRC6B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.371 | STS | Arina Puzriakova changed review comment from: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark; to: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Helen Brittain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.371 | STS | Arina Puzriakova Classified gene: STS as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.371 | STS | Arina Puzriakova Gene: sts has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.370 | STS | Arina Puzriakova Added comment: Comment on publications: Added publication (PMID: 32139392) describing psychiatric/behavioural phenotypes in patients with ichthyosis caused by X-linked deletions spanning STS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.370 | STS | Arina Puzriakova Publications for gene: STS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | NEMF |
Konstantinos Varvagiannis changed review comment from: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature; to: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides produced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration in mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | NEMF |
Konstantinos Varvagiannis changed review comment from: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could be ruled out that the de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature; to: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | NEMF |
Konstantinos Varvagiannis changed review comment from: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature; to: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could be ruled out that the de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | NEMF |
Konstantinos Varvagiannis gene: NEMF was added gene: NEMF was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NEMF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NEMF were set to 32934225 Phenotypes for gene: NEMF were set to Hypotonia; Global developmental delay; Intellectual disability; Axonal neuropathy; Ataxia; Abnormal brain imaging; Kyphosis; Scoliosis; Tremor; Respiratory distress Penetrance for gene: NEMF were set to Complete Review for gene: NEMF was set to GREEN Added comment: Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation. Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation. The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected). Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation. Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice. Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | PRKD1 |
Arina Puzriakova changed review comment from: Gene included previously in context of publication by Sifrim et al. (2016) (PMID: 27479907). However, re-evaluation of this paper showed that only two of the three patients had ID, which may possibly be associated with microcephaly. The two individuals carried a c.1774G>A and c.896T>G variant, respectively; however, a third patient also harbouring the c.1774G>A variant did not display any neuropsychological signs (or microcephaly) at 4.86 years (see supplementary table 12). A recent report (PMID: 32817298, 2020) describes two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, respectively. These patients shared cardiac and ectodermal abnormalities, as with the previously described patients; however, mental development was normal in both individuals.; to: Gene included previously in context of publication by Sifrim et al. (2016) (PMID: 27479907). However, re-evaluation of this paper showed that only two of the three patients had ID, which may possibly be associated with microcephaly. The two individuals carried a c.1774G>A and c.896T>G variant, respectively; however, a third patient also harbouring the c.1774G>A variant did not display any neuropsychological signs (or microcephaly) at 4.86 years (see supplementary table 12, and figure 3). A recent report (PMID: 32817298, 2020) describes two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, respectively. These patients shared cardiac and ectodermal abnormalities, as with the previously described patients; however, mental development was normal in both individuals. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | PRKD1 | Arina Puzriakova Classified gene: PRKD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | PRKD1 |
Arina Puzriakova Added comment: Comment on list classification: This gene has been flagged for review at the date of next GMS panel update (added 'for-review' tag). Only 2/5 patients exhibit features of ID, both of whom were also the only microcephalic cases, indicating the possibility of additional contributing factors. Therefore, a rating downgrade from Green to Amber may be warranted. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.369 | PRKD1 | Arina Puzriakova Gene: prkd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.368 | PRKD1 | Arina Puzriakova Publications for gene: PRKD1 were set to 27479907; 25529582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.367 | PRKD1 | Arina Puzriakova Tag for-review tag was added to gene: PRKD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.367 | PRKD1 | Arina Puzriakova reviewed gene: PRKD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27479907, 32817298; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.367 | CUL3 | Arina Puzriakova Phenotypes for gene: CUL3 were changed from to Global developmental delay; Intellectual disability; Autism Spectrum Disorder; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE, 614496 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.366 | CUL3 | Arina Puzriakova Publications for gene: CUL3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.365 | CUL3 | Arina Puzriakova Mode of inheritance for gene: CUL3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.364 | CUL3 | Arina Puzriakova Classified gene: CUL3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.364 | CUL3 | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber, as some cases reported with severe features of ID but not yet reaching the threshold for inclusion. Additional cases/publications would also enable clarification regarding the contribution of seizures to this phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.364 | CUL3 | Arina Puzriakova Gene: cul3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.363 | CUL3 | Arina Puzriakova commented on gene: CUL3: Literature search showed that CUL3 variants are often found in ASD patients, however the association with ID is much less discernible. Only two cases reported to date with severe ID features, but the same two individuals were also the only ones to present early-onset seizures. Therefore, it is difficult to distinguish whether these findings were independent of one another. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.363 | CUL3 | Arina Puzriakova changed review comment from: - PMID: 25969726 (2015) - Determined as a candidate gene following discovery of a de novo missense variant (c.2156A>G, p.H719R) in an autistic patient with mild ID, sleep disturbances and ADHD.; to: - PMID: 25969726 (2015) - Determined as a candidate gene following discovery of a de novo missense variant (c.2156A>G, p.H719R) in an autistic patient with mild ID, sleep disturbances, ADHD, and no seizures. No functional analysis was undertaken. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.363 | CUL3 | Arina Puzriakova reviewed gene: CUL3: Rating: ; Mode of pathogenicity: None; Publications: 25969726; Phenotypes: Autism spectrum disorder, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.363 | NHP2 | Arina Puzriakova Classified gene: NHP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.363 | NHP2 | Arina Puzriakova Added comment: Comment on list classification: Rating upgraded from Red to Amber as 2/3 cases described in literature present cognitive impairment. This does not yet meet the threshold for inclusion with a Green rating, but may be reviewed if further cases are published. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.363 | NHP2 | Arina Puzriakova Gene: nhp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.362 | NHP2 | Arina Puzriakova Phenotypes for gene: NHP2 were changed from Dyskeratosis congenita, autosomal recessive 2, 613987 to Dyskeratosis congenita, autosomal recessive 2, 613987; Høyeraal-Hreidarsson syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.361 | NHP2 | Arina Puzriakova Publications for gene: NHP2 were set to 25182133; 18523010; 25907943; 20301779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.360 | SETD1A | Zerin Hyder reviewed gene: SETD1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32346159; Phenotypes: Epilepsy, early-onset, with or without developmental delay, craniofacial dysmorphisms, behavioural/psychiatric abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.360 | CYP2U1 | Eleanor Williams Tag for-review tag was added to gene: CYP2U1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.360 | CYP2U1 | Eleanor Williams Classified gene: CYP2U1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.360 | CYP2U1 | Eleanor Williams Added comment: Comment on list classification: Leaving this gene as green for now, but after consultation with the Genomics England clinical team it was felt that it should be considered for downgrade to amber at the next GMS review. It is a spastic paraplegia gene and seems to mainly present in that manner. Amber rating would be appropriate as cognitive impairment is a feature and new cases may emerge which support that as a primary presentation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.360 | CYP2U1 | Eleanor Williams Gene: cyp2u1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.359 | NUP188 | Arina Puzriakova Phenotypes for gene: NUP188 were changed from to Sandestig-Stefanova syndrome, 618804 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.358 | NUP188 | Arina Puzriakova Publications for gene: NUP188 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.357 | NUP188 | Arina Puzriakova Mode of inheritance for gene: NUP188 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.356 | NUP188 | Arina Puzriakova Classified gene: NUP188 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.356 | NUP188 |
Arina Puzriakova Added comment: Comment on list classification: At least six unrelated families exhibiting a strikingly similar phenotype due to biallelic truncating variants in the NUP188 gene. Only 1/8 individuals survived beyond the first year of life and exhibited severe ID. It is anticipated that other surviving patients would likely present the same phenotype; however, for now NUP188 will be rated Amber on the ID panel, awaiting further publications to corroborate the relevance of this manifestation. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.356 | NUP188 | Arina Puzriakova Gene: nup188 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.355 | NUP188 | Arina Puzriakova reviewed gene: NUP188: Rating: GREEN; Mode of pathogenicity: None; Publications: 32021605, 32275884; Phenotypes: Sandestig-Stefanova syndrome, 618804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.355 | INTS6 | Arina Puzriakova Classified gene: INTS6 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.355 | INTS6 | Arina Puzriakova Added comment: Comment on list classification: The Red review by Konstantinos Varvagiannis supports the current Red rating of CPD. There is currently no evidence to support this gene-disease association, and therefore have kept rating as Red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.355 | INTS6 | Arina Puzriakova Gene: ints6 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.354 | CPD | Arina Puzriakova Classified gene: CPD as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.354 | CPD | Arina Puzriakova Added comment: Comment on list classification: The Red review by Konstantinos Varvagiannis supports the current Red rating of CPD. There is currently no evidence to support this gene-disease association, and therefore have kept rating as Red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.354 | CPD | Arina Puzriakova Gene: cpd has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.353 | KDM6B | Arina Puzriakova Classified gene: KDM6B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.353 | KDM6B | Arina Puzriakova Added comment: Comment on list classification: Sufficient number of patients to rate this gene GREEN at the next major review - psychomotor delay was consistently reported and was the key indication for clinical investigation in several cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.353 | KDM6B | Arina Puzriakova Gene: kdm6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.352 | KDM6B | Arina Puzriakova Phenotypes for gene: KDM6B were changed from Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505 to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.352 | KDM6B | Arina Puzriakova Phenotypes for gene: KDM6B were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.351 | KDM6B | Arina Puzriakova Publications for gene: KDM6B were set to 21937992 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.350 | KDM6B | Arina Puzriakova Mode of inheritance for gene: KDM6B was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.349 | KDM6B | Arina Puzriakova Tag for-review tag was added to gene: KDM6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.349 | KDM6B | Arina Puzriakova reviewed gene: KDM6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31124279; Phenotypes: Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.349 | HADH | Arina Puzriakova Classified gene: HADH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.349 | HADH | Arina Puzriakova Added comment: Comment on list classification: As ID is a secondary finding, reported in only a subset of patients, this gene should be downgraded from Green to Amber/Red at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.349 | HADH | Arina Puzriakova Gene: hadh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.348 | HADH | Arina Puzriakova Phenotypes for gene: HADH were changed from 3-HYDROXYACYL-COENZYME A DEHYDROGENASE DEFICIENCY to Hyperinsulinemic hypoglycemia, familial, 4, 609975; 3-hydroxyacyl-CoA dehydrogenase deficiency, 231530 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.347 | HADH | Arina Puzriakova Tag for-review tag was added to gene: HADH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.347 | HADH | Arina Puzriakova reviewed gene: HADH: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperinsulinemic hypoglycemia, familial, 4, 609975, 3-hydroxyacyl-CoA dehydrogenase deficiency, 231530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.347 | ADGRG6 | Arina Puzriakova Phenotypes for gene: ADGRG6 were changed from LETHAL CONGENITAL CONTRACTURE SYNDROME 9 to Lethal congenital contracture syndrome 9, 616503 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.346 | ADGRG6 | Arina Puzriakova Classified gene: ADGRG6 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.346 | ADGRG6 | Arina Puzriakova Gene: adgrg6 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.345 | AGL | Arina Puzriakova Classified gene: AGL as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.345 | AGL | Arina Puzriakova Gene: agl has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.344 | ALDOB | Arina Puzriakova Classified gene: ALDOB as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.344 | ALDOB | Arina Puzriakova Gene: aldob has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.343 | ADCY5 | Arina Puzriakova Classified gene: ADCY5 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.343 | ADCY5 | Arina Puzriakova Gene: adcy5 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.342 | ABAT | Arina Puzriakova Classified gene: ABAT as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.342 | ABAT | Arina Puzriakova Added comment: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team), it has been agreed that this gene should be upgraded from Amber to Green at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.342 | ABAT | Arina Puzriakova Gene: abat has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.341 | ABAT | Arina Puzriakova Tag for-review tag was added to gene: ABAT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.341 | ABAT | Arina Puzriakova reviewed gene: ABAT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GABA-transaminase deficiency, 613163; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.341 | ACADSB | Arina Puzriakova Phenotypes for gene: ACADSB were changed from to 2-methylbutyrylglycinuria, 610006 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.340 | ACADSB | Arina Puzriakova Mode of inheritance for gene: ACADSB was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.339 | ACADSB | Arina Puzriakova Classified gene: ACADSB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.339 | ACADSB |
Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber as DD has been reported, but only in a subset of symptomatic cases. Metabolic abnormalities should be a sufficient indication for testing, for which this gene is already rated Green. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.339 | ACADSB | Arina Puzriakova Gene: acadsb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.338 | ACADSB | Arina Puzriakova reviewed gene: ACADSB: Rating: ; Mode of pathogenicity: None; Publications: 30730842; Phenotypes: 2-methylbutyrylglycinuria, 610006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.338 | AHCY | Arina Puzriakova Publications for gene: AHCY were set to 15024124 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.337 | AHCY | Arina Puzriakova Classified gene: AHCY as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.337 | AHCY |
Arina Puzriakova Added comment: Comment on list classification: DD may occasionally be mild, however is an early and consistent finding amongst surviving patients. Inclusion on this panel may benefit detection of patients who would otherwise not be considered for testing via other routes (e.g. where metabolic abnormalities become apparent later). Therefore, recommending a GREEN rating at the next major review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.337 | AHCY | Arina Puzriakova Gene: ahcy has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | AHCY | Arina Puzriakova Tag for-review tag was added to gene: AHCY. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | AHCY | Arina Puzriakova commented on gene: AHCY: Added 'treatable' tag as some patients have shown improvement following dietary management (particularly methionine restriction and supplementation with creatine and phosphatidylcholine) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | AHCY | Arina Puzriakova Tag treatable tag was added to gene: AHCY. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | AHCY | Arina Puzriakova reviewed gene: AHCY: Rating: GREEN; Mode of pathogenicity: None; Publications: 15024124, 16435181, 16736098, 20852937, 22959829, 26095522, 26527160, 28779239, 30121674, 31957987; Phenotypes: Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, 613752; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | DDOST | Eleanor Williams Classified gene: DDOST as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | DDOST | Eleanor Williams Added comment: Comment on list classification: Leaving Green until the next major review, but the evidence does not support a green rating; this gene should be demoted to amber or red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.336 | DDOST | Eleanor Williams Gene: ddost has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.335 | DDOST | Eleanor Williams Tag for-review tag was added to gene: DDOST. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.335 | DDOST | Eleanor Williams reviewed gene: DDOST: Rating: AMBER; Mode of pathogenicity: None; Publications: 22305527; Phenotypes: ?Congenital disorder of glycosylation, type Ir, 614507, CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.335 | CYP2U1 | Eleanor Williams reviewed gene: CYP2U1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23176821; Phenotypes: Spastic paraplegia 56, autosomal recessive, 615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.335 | AGPS | Arina Puzriakova Phenotypes for gene: AGPS were changed from RHIZOMELIC CHONDRODYSPLASIA PUNCTATA TYPE 3 (RCDP3) to Rhizomelic chondrodysplasia punctata, type 3, 600121 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.334 | AGPS | Arina Puzriakova Publications for gene: AGPS were set to 7807941; 11152660 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.333 | AGPS | Arina Puzriakova Classified gene: AGPS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.333 | AGPS |
Arina Puzriakova Added comment: Comment on list classification: Though some relevant phenotypic features have been reported, the relationship with ID is not clear from literature. Patients are more likely to be recognised in context of the skeletal phenotype. Therefore, suggesting a rating downgrade from Green to Amber at the next major review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.333 | AGPS | Arina Puzriakova Gene: agps has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.332 | AGPS | Arina Puzriakova Tag for-review tag was added to gene: AGPS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.332 | AGPS | Arina Puzriakova reviewed gene: AGPS: Rating: AMBER; Mode of pathogenicity: None; Publications: 7807941, 11152660, 11152660, 21990100; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3, 600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.332 | MECP2 | Arina Puzriakova reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32469049; Phenotypes: Rett syndrome, 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.332 | UPF3B | Arina Puzriakova reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32667670; Phenotypes: Mental retardation, X-linked, syndromic 14, 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.332 | STAT1 | Arina Puzriakova Classified gene: STAT1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.332 | STAT1 | Arina Puzriakova Gene: stat1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.331 | STAT1 | Arina Puzriakova changed review comment from: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark; to: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Konstantinos Varvagiannis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.331 | RASA1 | Arina Puzriakova changed review comment from: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark; to: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Konstantinos Varvagiannis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.331 | ABCC6 | Arina Puzriakova Classified gene: ABCC6 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.331 | ABCC6 | Arina Puzriakova Gene: abcc6 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.330 | ABCC6 | Arina Puzriakova changed review comment from: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark; to: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Konstantinos Varvagiannis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.330 | RAD50 |
Arina Puzriakova changed review comment from: Comment on list classification: Borderline ID in second patient (at age 15 estimated IQ: 85). Therefore, keeping rating Red awaiting further cases to clarify the relevance of ID to the overall phenotype. ; to: Comment on list classification: Note uncertainty regarding ID in the first patient - PMID:1887849 states 'lack of mental retardation', while a later report PMID:19409520 describes 'mild to moderate retardation of psychomotor development'. ID was borderline in the second patient (at age 15 estimated IQ: 85). Therefore, keeping rating Red awaiting further cases to clarify the relevance of ID to the phenotype associated with RAD50 variants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.330 | RAD50 | Arina Puzriakova changed review comment from: Comment on list classification: Borderline ID in second patient (at age 15 estimated IQ: 85). Therefore, keeping rating Red awaiting further cases to ascertain the contribution of RAD50 variants to an ID phenotype.; to: Comment on list classification: Borderline ID in second patient (at age 15 estimated IQ: 85). Therefore, keeping rating Red awaiting further cases to clarify the relevance of ID to the overall phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.330 | RAD50 | Arina Puzriakova Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder,613078; NBSLD to Nijmegen breakage syndrome-like disorder, 613078 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.329 | RAD50 | Arina Puzriakova Publications for gene: RAD50 were set to 1887849; 19409520 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.328 | RAD50 | Arina Puzriakova Classified gene: RAD50 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.328 | RAD50 | Arina Puzriakova Added comment: Comment on list classification: Borderline ID in second patient (at age 15 estimated IQ: 85). Therefore, keeping rating Red awaiting further cases to ascertain the contribution of RAD50 variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.328 | RAD50 | Arina Puzriakova Gene: rad50 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.327 | WASHC4 | Arina Puzriakova Phenotypes for gene: WASHC4 were changed from Mental retardation, autosomal recessive 43, MIM #615817 to Mental retardation, autosomal recessive 43, 615817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.326 | WASHC4 | Arina Puzriakova Classified gene: WASHC4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.326 | WASHC4 | Arina Puzriakova Added comment: Comment on list classification: Rating Amber in view of mild/borderline ID in 2/3 families. Additional cases with a more significant manifestation of ID required before inclusion of WASHC4 on a diagnostic panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.326 | WASHC4 | Arina Puzriakova Gene: washc4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.325 | WASHC4 | Arina Puzriakova reviewed gene: WASHC4: Rating: ; Mode of pathogenicity: None; Publications: 21498477, 31953988; Phenotypes: Mental retardation, autosomal recessive 43, 615817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.325 | AFG3L2 | Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from SPINOCEREBELLAR ATAXIA 28 to Spastic ataxia 5, autosomal recessive, 614487 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.324 | AFG3L2 | Arina Puzriakova Classified gene: AFG3L2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.324 | AFG3L2 | Arina Puzriakova Added comment: Comment on list classification: This gene should be downgraded from Green to Red at the next major review, in accordance with the review by Zornitza Stark. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.324 | AFG3L2 | Arina Puzriakova Gene: afg3l2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.323 | AFG3L2 | Arina Puzriakova Publications for gene: AFG3L2 were set to 22022284 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.322 | AFG3L2 | Arina Puzriakova Tag for-review tag was added to gene: AFG3L2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.322 | RASA1 | Arina Puzriakova Classified gene: RASA1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.322 | RASA1 | Arina Puzriakova Gene: rasa1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.321 | LRP5 | Sarah Leigh Added comment: Comment on mode of inheritance: Other phenotypes associated with LRP5 variants (https://www.omim.org/entry/603506?search=LRP5&highlight=lrp5#geneMap) have monoallelic inheritance, however, these phenotypes are not relevant for this panel as ID has not been reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.321 | LRP5 | Sarah Leigh Mode of inheritance for gene: LRP5 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.320 | WDFY3 | Arina Puzriakova Classified gene: WDFY3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.320 | WDFY3 |
Arina Puzriakova Added comment: Comment on list classification: There is a sufficient number of cases with moderate ID to meet the threshold for inclusion on a diagnostic ID panel. Furthermore, ID is currently the most applicable clinical indication for detecting these cases using PanelApp panels. Therefore, recommending a rating upgrade from Amber to Green at the next major review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.320 | WDFY3 | Arina Puzriakova Gene: wdfy3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.319 | WDFY3 | Arina Puzriakova Tag for-review tag was added to gene: WDFY3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.319 | TRAK1 | Arina Puzriakova Phenotypes for gene: TRAK1 were changed from to Epileptic encephalopathy, early infantile, 68, 618201 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.318 | TRAK1 | Arina Puzriakova Publications for gene: TRAK1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.317 | TRAK1 | Arina Puzriakova Mode of inheritance for gene: TRAK1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.316 | TRAK1 |
Arina Puzriakova changed review comment from: Comment on list classification: Rating Amber - with ID seemingly following seizures, and being in association with a single recurrent variant, there is currently insufficient evidence to say that variants in this gene cause ID. This may, however, be reviewed if new evidence emerges. All cases have presented with seizures which should be an adequate indication for diagnostic testing (this gene is rated Green on the Genetic epilepsy syndromes (v2.152) panel).; to: Comment on list classification: Rating Amber - with ID seemingly following seizures, and being in association with a single recurrent variant, TRAK1 currently does not meet the threshold to say that variants cause ID. This may, however, be reviewed if new evidence emerges. All cases have presented with seizures which should be an adequate indication for diagnostic testing (this gene is rated Green on the Genetic epilepsy syndromes (v2.152) panel). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.316 | TRAK1 | Arina Puzriakova Classified gene: TRAK1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.316 | TRAK1 |
Arina Puzriakova Added comment: Comment on list classification: Rating Amber - with ID seemingly following seizures, and being in association with a single recurrent variant, there is currently insufficient evidence to say that variants in this gene cause ID. This may, however, be reviewed if new evidence emerges. All cases have presented with seizures which should be an adequate indication for diagnostic testing (this gene is rated Green on the Genetic epilepsy syndromes (v2.152) panel). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.316 | TRAK1 | Arina Puzriakova Gene: trak1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | TRAK1 | Arina Puzriakova reviewed gene: TRAK1: Rating: ; Mode of pathogenicity: None; Publications: 28940097, 28364549, 29846532; Phenotypes: Epileptic encephalopathy, early infantile, 68, 618201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | SLC12A2 | Konstantinos Varvagiannis reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | ZMYM2 |
Konstantinos Varvagiannis gene: ZMYM2 was added gene: ZMYM2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZMYM2 were set to 32891193 Phenotypes for gene: ZMYM2 were set to Abnormality of the urinary system; Global developmental delay; Intellectual disability; Microcephaly; Abnormality of the cardiovascular system; Autism; Seizures; Abnormality of the head or neck; Abnormality of the nail; Small hand; Short foot; Clinodactyly Penetrance for gene: ZMYM2 were set to unknown Review for gene: ZMYM2 was set to AMBER Added comment: Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features. DD and ID were reported in some of the families described to date as summarized below. You might consider inclusion with green/amber rating in the ID panel and green in the panel for CAKUT. -- Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants. [Article not reviewed in detail]. Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly. 14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family. The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT. ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body). It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors. The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | DHX37 | Arina Puzriakova changed review comment from: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least 6 unrelated cases with ID associated with variants in this gene.; to: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least 6 unrelated cases with ID associated with variants in this gene (albeit association with monoallelic variants in 2 cases warrants further investigation). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | DHX37 | Arina Puzriakova Classified gene: DHX37 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | DHX37 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least 6 unrelated cases with ID associated with variants in this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.315 | DHX37 | Arina Puzriakova Gene: dhx37 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.314 | DHX37 | Arina Puzriakova Tag for-review tag was added to gene: DHX37. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.314 | DHX37 | Arina Puzriakova reviewed gene: DHX37: Rating: GREEN; Mode of pathogenicity: None; Publications: 26539891, 31256877; Phenotypes: Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, 618731; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.314 | LMNB1 |
Konstantinos Varvagiannis gene: LMNB1 was added gene: LMNB1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: LMNB1 were set to 32910914 Phenotypes for gene: LMNB1 were set to Global developmental delay; Intellectual disability; Microcephaly; Short stature; Seizures; Abnormality of the corpus callosum; Cortical gyral simplification; Feeding difficulties; Scoliosis Penetrance for gene: LMNB1 were set to unknown Mode of pathogenicity for gene: LMNB1 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: LMNB1 was set to GREEN Added comment: Cristofoli et al (2020 - PMID: 32910914) report 7 individuals (from 5 families) harboring mostly de novo LMNB1 variants. The common phenotype consisted of primary microcephaly (7/7 ranging from -4.4 to -10 SD), DD/ID (7/7), relative short stature in most (+0.7 to -4 SD). Additional features included brain MRI abnormalities (abnormal CC in 3, simplified gyral pattern in 3, small structurally normal brain, etc), seizures (4 individuals from 2 families), limb spasticity (1/7), cortical visual impairment (in 3), feeding difficulties (5/7), scoliosis (4/7). Non-overlapping dysmorphic features were reported in some. Variants were identified by WES or custom-designed gene panel and included 3 missense variants, 1 in-frame deletion and a splice variant. The in-frame deletion was inherited from a similarly affected parent in whom the variant occurred as a dn event. The splice SNV(NM_005573.3:c.939+1G>A) occurred in 3 sibs and was present as mosaic variant (15%) in the parent. This variant was predicted to result to extension of exon 5 by 6 amino-acids (samples were unavailable for mRNA studies). LMNB1 encodes a B-type lamin (the other being encoded by LMNB2). A- and B- type lamins are major components of the nuclear lamina. As the authors comment, LMNB1 is expressed in almost all cell types beginning at the earliest stages of development. Lamin-deficient mouse models support an essential role of B-type lamins in organogenesis, neuronal migration, patterning during brain development. Functional studies performed, demonstrated impaired formation of LMNB1 nuclear lamina in LMNB1-null HeLa cells transfected with cDNAs for 3 missense variants. Two variants (Lys33Glu/Arg42Trp) were shown to result in decreased nuclear localization with increased abundance in the cytosolic fraction. In patient derived LCLs these variants led to abnormal nuclear morphology. A missense variant in another domain (Ala152Gly - 1st coil domain) resulted also in lower abundance of lamin B1, irregular lamin A/C nuclear lamina, as well as more condensed nuclei (HeLa cells). LMNB1 duplications or missense mutations increasing LMNB1 expression are associated with a different presentation of AD leuodystrophy. A variant previously associated with leukodystrophy (Arg29Trp) was shown to behave differently (present in the nuclear extract but not in the cytosol, lamin B1 to A/C ratio in nuclear extract was not significantly altered compared to wt as was the case for Arg42Trp, Lys33Glu). Given the pLI score of 0.55 as well as the phenotype of individuals with deletions (not presenting microcephaly) the authors predict that a dominant-negative effect applies (rather than haploinsufficiency). Consider inclusion in the following panels : DD/ID (green), epilepsy (amber - 4 of 7 patients belonging to 2 families), primary microcephaly (green), callosome (amber/green - 3 individuals belonging to 3 families), mendeliome (green), etc. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.314 | SPTBN4 | Konstantinos Varvagiannis edited their review of gene: SPTBN4: Added comment: ** Consider also the GeneReview on this disorder - PMID : 32672909; Changed publications: 28540413, 28940097, 29861105, 31230720, 31857255, 32672909 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.314 | CAMK2G | Arina Puzriakova Publications for gene: CAMK2G were set to 26350204; 24896178; 23033978 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.313 | CAMK2G | Arina Puzriakova Phenotypes for gene: CAMK2G were changed from to Mental retardation, autosomal dominant 59, 618522 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.312 | CAMK2G | Arina Puzriakova Mode of pathogenicity for gene: CAMK2G 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.311 | CAMK2G | Arina Puzriakova Classified gene: CAMK2G as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.311 | CAMK2G | Arina Puzriakova Added comment: Comment on list classification: Rating has been upgraded from Red to Amber based on the review by Konstantinos Varvagiannis - two unrelated individuals with severe ID, associated with de novo CAMK2G variants, with addition of functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.311 | CAMK2G | Arina Puzriakova Gene: camk2g has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.310 | FIBP | Arina Puzriakova Classified gene: FIBP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.310 | FIBP | Arina Puzriakova Added comment: Comment on list classification: Rating upgraded from Red to Amber based on review by Zornitza Stark. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.310 | FIBP | Arina Puzriakova Gene: fibp has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.309 | FIBP | Arina Puzriakova Phenotypes for gene: FIBP were changed from Thauvin-Robinet-Faivre syndrome to Thauvin-Robinet-Faivre syndrome, 617107 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.308 | FIBP | Arina Puzriakova Added comment: Comment on publications: Two publications (PMID: 26660953; 27183861) describing four individuals from two unrelated families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.308 | FIBP | Arina Puzriakova Publications for gene: FIBP were set to 26660953 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.307 | TANC2 | Arina Puzriakova Tag watchlist tag was added to gene: TANC2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.307 | TANC2 | Arina Puzriakova Phenotypes for gene: TANC2 were changed from NDD syndrome; Neurodevelopmental Disorder; Intellectual disability; Childhood speech delay; Childhood motor delay to Intellectual developmental disorder with autistic features and language delay, with or without seizures, 618906 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.306 | VAMP1 | Arina Puzriakova Tag watchlist tag was added to gene: VAMP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.306 | VAMP1 | Arina Puzriakova Phenotypes for gene: VAMP1 were changed from congenital myasthenic syndrome (CMS) and delayed development to Myasthenic syndrome, congenital, 25, 618323 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.305 | VAMP1 | Arina Puzriakova Publications for gene: VAMP1 were set to 28253535 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.304 | VAMP1 | Arina Puzriakova Classified gene: VAMP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.304 | VAMP1 |
Arina Puzriakova Added comment: Comment on list classification: Literature search revealed that developmental delay primarily affects motor function, and it is unclear whether patients exhibit any cognitive deficit. Additional cases would help delineate the association with this phenotype. Therefore, recommending a rating downgrade from Green to Amber/Red at the next major review, awaiting further publications/clinical evidence. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.304 | VAMP1 | Arina Puzriakova Gene: vamp1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.303 | VAMP1 | Arina Puzriakova Tag for-review tag was added to gene: VAMP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.303 | TRIM32 | Arina Puzriakova Tag for-review tag was added to gene: TRIM32. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.303 | TRIM32 | Arina Puzriakova Phenotypes for gene: TRIM32 were changed from BARDET-BIEDL SYNDROME TYPE 11 (BBS11) to Bardet-Biedl syndrome 11, 615988 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.302 | TRIM32 | Arina Puzriakova Publications for gene: TRIM32 were set to 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.301 | TRIM32 | Arina Puzriakova Classified gene: TRIM32 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.301 | TRIM32 | Arina Puzriakova Added comment: Comment on list classification: Recommended Green-to-Red rating downgrade on the next major review - only one family reported to date for association with BBS. Currently also Red on the Bardet-Biedl Syndrome (Version 1.5) gene panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.301 | TRIM32 | Arina Puzriakova Gene: trim32 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.300 | VARS2 | Arina Puzriakova Classified gene: VARS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.300 | VARS2 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - >3 unrelated families with different variants. Severe psychomotor delay was an early and significant manifestation on clinical evaluation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.300 | VARS2 | Arina Puzriakova Gene: vars2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.299 | VARS2 | Arina Puzriakova Tag for-review tag was added to gene: VARS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.299 | SUCLA2 | Arina Puzriakova Classified gene: SUCLA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.299 | SUCLA2 |
Arina Puzriakova Added comment: Comment on list classification: Although sufficient number of cases with relevant clinical presentation, psychomotor delay is a component of a broader phenotype. Patients are more likely to be recognised via other routes (Metabolic/White Matter Disorders/Mitochondrial) - SUCLA2 is already Green on these PanelApp panels. Therefore, rating Amber on the ID panel. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.299 | SUCLA2 | Arina Puzriakova Gene: sucla2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.298 | FRY | Arina Puzriakova Publications for gene: FRY were set to 21937992 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.297 | FRY | Arina Puzriakova Classified gene: FRY as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.297 | FRY | Arina Puzriakova Gene: fry has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.296 | ELN | Arina Puzriakova Classified gene: ELN as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.296 | ELN | Arina Puzriakova Gene: eln has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ELN | Arina Puzriakova changed review comment from: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark; to: Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Konstantinos Varvagiannis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ATP1A3 | Zornitza Stark edited their review of gene: ATP1A3: Added comment: Four additional individuals with dystonia, dysmorphism, encephalopathy with developmental delay, brain MRI abnormalities always including cerebellar hypoplasia, no hemiplegia, and neonatal onset. All had de novo missense variants. All are described to have global developmental delay, hence supporting upgrade in rating on this panel.; Changed rating: GREEN; Changed publications: https://doi.org/10.1212/NXG.0000000000000466; Changed phenotypes: Alternating hemiplegia of childhood 2, MIM#614820, Neurodevelopmental disorder; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | WASHC4 |
Zornitza Stark gene: WASHC4 was added gene: WASHC4 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WASHC4 were set to 31953988; 21498477 Phenotypes for gene: WASHC4 were set to Mental retardation, autosomal recessive 43, MIM #615817 Review for gene: WASHC4 was set to GREEN gene: WASHC4 was marked as current diagnostic Added comment: Three unrelated families reported. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | RAD50 | Zornitza Stark reviewed gene: RAD50: Rating: AMBER; Mode of pathogenicity: None; Publications: 32212377; Phenotypes: Nijmegen breakage syndrome-like disorder, MIM# 613078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ATP1A2 | Sarah Leigh commented on gene: ATP1A2: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ATP1A2 | Sarah Leigh Tag for-review tag was added to gene: ATP1A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ATP1A2 | Sarah Leigh edited their review of gene: ATP1A2: Added comment: Associated with phenotype in OMIM and in G2P for MIGRAINE, FAMILIAL HEMIPLEGIC, ATP1A2-related. Three variants associated with congnitive impairment in 2/7 and 1/5 members of two families with Migraine, familial hemiplegic, 2 602481. At least 12 variants have been reported in Migraine, familial hemiplegic, 2 602481 families (PMID 15159495). An additional variant was reported in a case of Alternating hemiplegia of childhood 1, 104290 with impared cognitive function (PMID 29610157).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ANKH | Sarah Leigh commented on gene: ANKH: There is no evidence for this gene to be rated GREEN, it should be rated RED at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ANKH | Sarah Leigh reviewed gene: ANKH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.295 | ANKH | Sarah Leigh Publications for gene: ANKH were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.294 | ANKH | Sarah Leigh Tag for-review tag was added to gene: ANKH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.294 | TNR | Arina Puzriakova Classified gene: TNR as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.294 | TNR | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least 7 unrelated cases with cognitive impairment associated with variants in this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.294 | TNR | Arina Puzriakova Gene: tnr has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.293 | TNR | Arina Puzriakova reviewed gene: TNR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22730557, 32099069; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.293 | EARS2 | Sarah Leigh Tag for-review tag was added to gene: EARS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.293 | EARS2 | Sarah Leigh edited their review of gene: EARS2: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.293 | EARS2 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 15 variants reported in at least 12 unrelated cases, with variable degrees of psycomotor motor delay or regression and little or no language.; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 14 variants reported in at least 11 unrelated cases, with variable degrees of psycomotor motor delay or regression and little or no language. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.293 | EARS2 | Sarah Leigh Publications for gene: EARS2 were set to 22492562 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.292 | EARS2 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 14 variants reported in at least 11 unrelated cases, with variable degrees of psycomotor motor delay or regression and little or no language.; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 15 variants reported in at least 12 unrelated cases, with variable degrees of psycomotor motor delay or regression and little or no language. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.292 | EARS2 | Sarah Leigh Classified gene: EARS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.292 | EARS2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 14 variants reported in at least 11 unrelated cases, with variable degrees of psycomotor motor delay or regression and little or no language. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.292 | EARS2 | Sarah Leigh Gene: ears2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.291 | SLC12A2 | Arina Puzriakova Publications for gene: SLC12A2 were set to 28940097; 30740830; 32754646 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.290 | SLC12A2 | Arina Puzriakova Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.289 | SLC12A2 | Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least three unrelated cases presenting a relevant phenotype in association with biallelic variants in SLC12A2.; to: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least nine unrelated cases presenting a relevant phenotype in association with variants in SLC12A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.289 | SLC12A2 | Arina Puzriakova edited their review of gene: SLC12A2: Changed publications: 28940097, 30740830, 32754646, 32658972; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.289 | SLC12A2 |
Arina Puzriakova changed review comment from: - PMID: 28940097 (2017) - SLC12A2 first identified as a novel candidate gene in a 3.3-year-old male with GDD, failure to thrive, hypotonia, microcephaly, neonatal respiratory distress, recurrent aspiration pneumonia, and osteopenia. Sequencing revealed a homozygous variant (c.2617-2A>G) that segregated within the family. - PMID: 30740830 (2019) - Homozygous 22kb deletion identified in a 5-year-old male with GDD, sensorineural hearing loss, gastrointestinal abnormalities, early postnatal respiratory distress, generalised hypotonia, and absent salivation. Neuropsychological testing demonstrated profound delays in all developmental areas, with skills ranging from 1 to 6 months. The deletion was the result of uniparental paternal isodisomy. Functional studies using patient-derived fibroblasts showed truncated SLC12A2 transcripts and markedly reduced protein levels compared to control. Knockout mouse model recapitulated phenotypic features such as deafness, abnormal neuronal growth and migration, gastrointestinal abnormalities, and absent salivation. - PMID: 32754646 (2020) - Compound heterozygous variants (c.1431delT and c.2006-1G>A) were identified in two sibs. The proband, an 8-year-old girl, presented a severe neurodevelopmental disorder (including severe ID), hearing impairment, gastrointestinal problems, hypotonia, and absent tear fluid, saliva, and sweat. Phenotypic overlap was noted in an affected older sister, who died at 22 days of age.; to: - PMID: 28940097 (2017) - SLC12A2 first identified as a novel candidate gene in a 3.3-year-old male with GDD, failure to thrive, hypotonia, microcephaly, neonatal respiratory distress, recurrent aspiration pneumonia, and osteopenia. Sequencing revealed a homozygous variant (c.2617-2A>G) that segregated within the family. - PMID: 30740830 (2019) - Homozygous 22kb deletion identified in a 5-year-old male with GDD, sensorineural hearing loss, gastrointestinal abnormalities, early postnatal respiratory distress, generalised hypotonia, and absent salivation. Neuropsychological testing demonstrated profound delays in all developmental areas, with skills ranging from 1 to 6 months. The deletion was the result of uniparental paternal isodisomy. Functional studies using patient-derived fibroblasts showed truncated SLC12A2 transcripts and markedly reduced protein levels compared to control. Knockout mouse model recapitulated phenotypic features such as deafness, abnormal neuronal growth and migration, gastrointestinal abnormalities, and absent salivation. - PMID: 32754646 (2020) - Compound heterozygous variants (c.1431delT and c.2006-1G>A) were identified in two sibs. The proband, an 8-year-old girl, presented a severe neurodevelopmental disorder (including severe ID), hearing impairment, gastrointestinal problems, hypotonia, and absent tear fluid, saliva, and sweat. Phenotypic overlap was noted in an affected older sister, who died at 22 days of age. - PMID: 32658972 (2020) - Six unrelated children, all with mild-severe ID/DD, associated with de novo variants in SLC12A2. Additional clinical features included bilateral sensorineural hearing loss (2/6), abnormalities on brain MRI (2/4), and cerebral palsy (2/6). Some functional data in Xenopus laevis oocytes, indicating a role of SLC12A2 in neurogenesis. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.289 | DHX37 |
Zornitza Stark gene: DHX37 was added gene: DHX37 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DHX37 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DHX37 were set to 26539891; 31256877 Phenotypes for gene: DHX37 were set to Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731 Review for gene: DHX37 was set to GREEN gene: DHX37 was marked as current diagnostic Added comment: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype. Green for bi-allelic disease Much less clear association between mono-allelic variants and ID, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo. No mechanism for mono-allelic vs bi-allelic disease proposed. Overall, Red for mono-allelic variants causing a neurodevelopmental phenotype at this stage. Note there is a separate association between mono allelic variants and DSD. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.289 | SLC12A2 | Arina Puzriakova Publications for gene: SLC12A2 were set to 30740830 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.288 | SLC12A2 | Arina Puzriakova Classified gene: SLC12A2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.288 | SLC12A2 | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least three unrelated cases presenting a relevant phenotype in association with biallelic variants in SLC12A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.288 | SLC12A2 | Arina Puzriakova Gene: slc12a2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.287 | SLC12A2 | Arina Puzriakova Tag for-review tag was added to gene: SLC12A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.287 | SLC12A2 | Arina Puzriakova reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 30740830, 32754646; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.287 | EXOC7 | Arina Puzriakova Classified gene: EXOC7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.287 | EXOC7 |
Arina Puzriakova Added comment: Comment on list classification: Though mild-severe DD is reported in all surviving patients to date (4 individuals from 2 families), additional unrelated cases required before inclusion on a diagnostic panel. Therefore, rating Amber in anticipation of further publications (added to watchlist). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.287 | EXOC7 | Arina Puzriakova Gene: exoc7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.286 | EXOC7 | Arina Puzriakova Tag watchlist tag was added to gene: EXOC7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.286 | HNRNPH1 | Arina Puzriakova Tag for-review tag was added to gene: HNRNPH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.286 | HNRNPH1 | Arina Puzriakova changed review comment from: Comment on list classification: Two studies report de novo variants in at least 7 unrelated cases with moderate-severe GDD/ID.; to: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - two studies report de novo variants in at least 7 unrelated cases with moderate-severe GDD/ID. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.286 | HNRNPH1 | Arina Puzriakova Classified gene: HNRNPH1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.286 | HNRNPH1 | Arina Puzriakova Added comment: Comment on list classification: Two studies report de novo variants in at least 7 unrelated cases with moderate-severe GDD/ID. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.286 | HNRNPH1 | Arina Puzriakova Gene: hnrnph1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.285 | HARS | Arina Puzriakova commented on gene: HARS: Added new-gene-name tag, new approved HGNC gene symbol for HARS is HARS1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.285 | HARS | Arina Puzriakova Tag new-gene-name tag was added to gene: HARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.285 | HARS | Arina Puzriakova Classified gene: HARS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.285 | HARS | Arina Puzriakova Added comment: Comment on list classification: Relevant phenotype for this panel but additional cases required. Therefore, rating Amber in anticipation of further publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.285 | HARS | Arina Puzriakova Gene: hars has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.284 | CCDC88A | Arina Puzriakova Classified gene: CCDC88A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.284 | CCDC88A | Arina Puzriakova Added comment: Comment on list classification: This gene has been upgraded from Red to Amber based on the external reviews by Konstantinos Varvagiannis and Zornitza Stark. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.284 | CCDC88A | Arina Puzriakova Gene: ccdc88a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.283 | CCDC174 | Arina Puzriakova Classified gene: CCDC174 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.283 | CCDC174 |
Arina Puzriakova Added comment: Comment on list classification: Rating Red as only one founder variant reported to-date in a single publication - currently no evidence that other variants in this gene are disease-causing. Added 'founder-effect' tag |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.283 | CCDC174 | Arina Puzriakova Gene: ccdc174 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.282 | CCDC174 | Arina Puzriakova Tag founder-effect tag was added to gene: CCDC174. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.282 | TAF1C | Arina Puzriakova Classified gene: TAF1C as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.282 | TAF1C | Arina Puzriakova Gene: taf1c has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.281 | PAK3 | Arina Puzriakova reviewed gene: PAK3: Rating: ; Mode of pathogenicity: None; Publications: 31943058; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.281 | TRAPPC2L | Arina Puzriakova Classified gene: TRAPPC2L as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.281 | TRAPPC2L | Arina Puzriakova Added comment: Comment on list classification: Rating Amber as additional cases required to delineate the genotype-phenotype relationship. Total of three families, but two share a founder variant, and there are some disparities between the clinical presentations reported in the two publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.281 | TRAPPC2L | Arina Puzriakova Gene: trappc2l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.280 | TRAPPC2L |
Arina Puzriakova gene: TRAPPC2L was added gene: TRAPPC2L was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TRAPPC2L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC2L were set to 30120216; 32843486 Phenotypes for gene: TRAPPC2L were set to Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331 Review for gene: TRAPPC2L was set to AMBER Added comment: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P. PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect. The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11. PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family. Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.279 | LMBRD2 | Arina Puzriakova Classified gene: LMBRD2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.279 | LMBRD2 | Arina Puzriakova Added comment: Comment on list classification: There is a sufficient number of unrelated cases to rate this gene GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.279 | LMBRD2 | Arina Puzriakova Gene: lmbrd2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.278 | LMBRD2 | Arina Puzriakova Tag for-review tag was added to gene: LMBRD2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.278 | SUPT16H | Arina Puzriakova Publications for gene: SUPT16H were set to http://dx.doi.org/10.1136/jmedgenet-2019-106193 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.277 | SUPT16H | Arina Puzriakova Classified gene: SUPT16H as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.277 | SUPT16H | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next major review - at least four unrelated individuals with GDD/ID (plus another additional patient with a deletion, albeit encompassing other potentially clinically relevant genes). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.277 | SUPT16H | Arina Puzriakova Gene: supt16h has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.276 | SUPT16H | Arina Puzriakova Tag for-review tag was added to gene: SUPT16H. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.276 | ADARB1 | Arina Puzriakova Publications for gene: ADARB1 were set to 32220291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.275 | ADARB1 | Arina Puzriakova Phenotypes for gene: ADARB1 were changed from Intellectual disability; microcephaly; seizures to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.274 | ADARB1 | Arina Puzriakova edited their review of gene: ADARB1: Added comment: PMID: 32719099 (2020) - Three additional patients from two consanguineous families with novel biallelic variants in the ADARB1 gene. All affected individuals presented global DD, severe-profound ID, intractable early infantile-onset seizures, severe microcephaly, axial hypotonia and progressive appendicular spasticity. In vitro RNA editing assays showed that both variants resulted in severe impairment or loss of ADAR2 enzymatic activity.; Changed publications: 32220291, 32719099 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.274 | HARS | Zornitza Stark edited their review of gene: HARS: Changed publications: 32333447 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.274 | TKFC | Arina Puzriakova Classified gene: TKFC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.274 | TKFC | Arina Puzriakova Added comment: Comment on list classification: Additional cases required before inclusion on a diagnostic panel (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.274 | TKFC | Arina Puzriakova Gene: tkfc has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.273 | TKFC | Arina Puzriakova Phenotypes for gene: TKFC were changed from Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, 618805 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.272 | TKFC | Arina Puzriakova Tag watchlist tag was added to gene: TKFC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.272 | TKFC | Arina Puzriakova reviewed gene: TKFC: Rating: AMBER; Mode of pathogenicity: None; Publications: 32004446; Phenotypes: Triokinase and FMN cyclase deficiency syndrome, 618805; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.272 | TP73 | Arina Puzriakova Classified gene: TP73 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.272 | TP73 | Arina Puzriakova Added comment: Comment on list classification: Rating Red as gene only distinguished due to multiple hits in same candidate gene - patients display discordant phenotype and DD only reported in one patient. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.272 | TP73 | Arina Puzriakova Gene: tp73 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.271 | TP73 | Arina Puzriakova reviewed gene: TP73: Rating: RED; Mode of pathogenicity: None; Publications: 31130284; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.271 | SMG8 | Arina Puzriakova Classified gene: SMG8 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.271 | SMG8 | Arina Puzriakova Added comment: Comment on list classification: Rating Red as gene only distinguished due to multiple hits in same candidate gene; however, patients display discordant phenotype and ID only reported in one patient. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.271 | SMG8 | Arina Puzriakova Gene: smg8 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.270 | SMG8 | Arina Puzriakova reviewed gene: SMG8: Rating: RED; Mode of pathogenicity: None; Publications: 31130284; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.270 | RAP1GDS1 | Arina Puzriakova Tag founder-effect tag was added to gene: RAP1GDS1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.270 | RAP1GDS1 | Arina Puzriakova Classified gene: RAP1GDS1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.270 | RAP1GDS1 | Arina Puzriakova Added comment: Comment on list classification: The same variant identified in two families from the region, indicating a possible founder effect. Therefore rated Red as there is not currently enough evidence that other variants in the RAP1GDS1 gene are disease causing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.270 | RAP1GDS1 | Arina Puzriakova Gene: rap1gds1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.269 | RAP1GDS1 | Arina Puzriakova reviewed gene: RAP1GDS1: Rating: ; Mode of pathogenicity: None; Publications: 32431071; Phenotypes: Intellectual disability, Global developmental delay, Hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.269 | PDCD6IP | Arina Puzriakova Classified gene: PDCD6IP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.269 | PDCD6IP | Arina Puzriakova Added comment: Comment on list classification: Phenotype is relevant to this panel but additional cases required to validate pathogenicity of variants in this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.269 | PDCD6IP | Arina Puzriakova Gene: pdcd6ip has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 |
Arina Puzriakova changed review comment from: Comment on list classification: Although the phenotype is relevant for this panel, additional cases would help determine the aetiology of the ID presentation. This gene has been added to other panels (Malformations of cortical development/Epilepsy), in view of which these patients are more likely to be recognised. Rating Amber, awaiting further publications (added to watchlist).; to: Comment on list classification: Although the phenotype is relevant for this panel, additional cases would help determine the aetiology of the ID presentation. This gene has been added to other panels (Malformations of cortical development/Epilepsy/Microcephaly), in view of which these patients are more likely to be recognised. Rating Amber, awaiting further publications (added to watchlist). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 | Arina Puzriakova Classified gene: TUBGCP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 |
Arina Puzriakova Added comment: Comment on list classification: Although the phenotype is relevant for this panel, additional cases would help determine the aetiology of the ID presentation. This gene has been added to other panels (Malformations of cortical development/Epilepsy), in view of which these patients are more likely to be recognised. Rating Amber, awaiting further publications (added to watchlist). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 | Arina Puzriakova Gene: tubgcp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 | Arina Puzriakova Classified gene: TUBGCP2 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 |
Arina Puzriakova Added comment: Comment on list classification: Although the phenotype is relevant for this panel, additional cases would help determine the aetiology of the ID presentation. This gene has been added to other panels (Malformations of cortical development/Epilepsy), in view of which these patients are more likely to be recognised. Rating Amber, awaiting further publications (added to watchlist). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.268 | TUBGCP2 | Arina Puzriakova Gene: tubgcp2 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.267 | TUBGCP2 | Arina Puzriakova Tag watchlist tag was added to gene: TUBGCP2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.267 | TUBGCP2 | Arina Puzriakova reviewed gene: TUBGCP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31630790; Phenotypes: Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.267 | PPP1R12A | Arina Puzriakova Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome, 618820 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.266 | PPP1R12A | Arina Puzriakova Classified gene: PPP1R12A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.266 | PPP1R12A | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - DD reported in at least 7 unrelated patients with PPP1R12A variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.266 | PPP1R12A | Arina Puzriakova Gene: ppp1r12a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.265 | PPP1R12A | Arina Puzriakova Tag for-review tag was added to gene: PPP1R12A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.265 | PPP1R12A |
Arina Puzriakova changed review comment from: PMID: 31883643 (2020) - Screening cohorts of patients with holoprosencephaly and patients with disorders of sex development revealed 12 unrelated individuals with de novo LoF variants in the PPP1R12A gene. Variants were associated with a broad spectrum of manifestations, and a clear genotype-phenotype correlation was not observed - most commonly presentation included either malformations of the brain or the genitourinary tract (two individuals exhibited both brain and genitourinary anomalies). 7/12 individuals exhibited developmental delay, which warrants inclusion on this panel.; to: Associated with phenotype in OMIM, and a probable gene for PPP1R12A-related Holoprosencephaly Spectrum and Urogenital Malformations in G2P. PMID: 31883643 (2020) - Screening cohorts of patients with holoprosencephaly and patients with disorders of sex development revealed 12 unrelated individuals with de novo LoF variants in the PPP1R12A gene. Variants were associated with a broad spectrum of manifestations, and a clear genotype-phenotype correlation was not observed - most commonly presentation included either malformations of the brain or the genitourinary tract (two individuals exhibited both brain and genitourinary anomalies). 7/12 individuals exhibited developmental delay, which warrants inclusion on this panel. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.265 | PPP1R12A | Arina Puzriakova reviewed gene: PPP1R12A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31883643; Phenotypes: Genitourinary and/or/brain malformation syndrome, 618820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.265 | TRNT1 | Arina Puzriakova Tag for-review tag was added to gene: TRNT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.265 | TRNT1 | Arina Puzriakova Publications for gene: TRNT1 were set to 25193871; 23553769; 29170023; 27389523 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.264 | TRNT1 | Arina Puzriakova Classified gene: TRNT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.264 | TRNT1 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - sufficient number of cases with (mild-profound) developmental delay, associated with biallelic variants in TRNT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.264 | TRNT1 | Arina Puzriakova Gene: trnt1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.263 | TENM3 | Arina Puzriakova Classified gene: TENM3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.263 | TENM3 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - sufficient unrelated cases with an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.263 | TENM3 | Arina Puzriakova Gene: tenm3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | TENM3 | Arina Puzriakova Tag for-review tag was added to gene: TENM3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | TENM3 | Arina Puzriakova reviewed gene: TENM3: Rating: ; Mode of pathogenicity: None; Publications: 22766609, 27103084, 30513139, 29753094; Phenotypes: Microphthalmia, syndromic 15, 615145, ?Microphthalmia, isolated, with coloboma 9, 615145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | KAT5 | Konstantinos Varvagiannis reviewed gene: KAT5: 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: 32822602; Phenotypes: Severe global developmental delay, Intellectual disability, Seizures, Microcephaly, Behavioral abnormality, Sleep disturbance, Morphological abnormality of the central nervous system, Short stature, Oral cleft, Abnormality of the face; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | LMBRD2 |
Konstantinos Varvagiannis gene: LMBRD2 was added gene: LMBRD2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: LMBRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: LMBRD2 were set to 32820033; https://doi.org/10.1101/797787 Phenotypes for gene: LMBRD2 were set to Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye Penetrance for gene: LMBRD2 were set to unknown Review for gene: LMBRD2 was set to AMBER Added comment: You may consider inclusion with green (13 individuals with dn missense SNVs overall, overlapping features for 10 with available phenotype / a recurring variant has been identified in 2 different studies) or amber rating (role of the gene not known, no variant studies, animal model probably not available). ► Malhotra et al (2020 - PMID: 32820033) report on 10 unrelated individuals with de novo missense LMBRD2 variants. Features included DD (9/10), ID (6/8 of relevant age), microcephaly (7/10), seizures (5/10 - >=3 different variants), structural brain abnormalities (e.g. thin CC in 6/9), highly variable ocular abnormalities (5/10) and dysmorphic features in some (7/10 - nonspecific). All had variable prior non-diagnostic genetic tests (CMA, gene panel, mendeliome, karyotype). WES/WGS revealed LMBRD2 missense variants, in all cases de novo. A single individual had additional variants with weaker evidence of pathogenicity. 5 unique missense SNVs and 2 recurrent ones (NM_001007527:c.367T>C - p.Trp123Arg / c.1448G>A - p.Arg483His) were identified. These occurred in different exons. Variants were not present in gnomAD and all had several in silico predictions in favor of a deleterious effect. There was phenotypic variability among individuals with the same variant (e.g. seizures in 1/3 and microchephaly in 2/3 of those harboring R483H). The gene has a pLI of 0 (although o/e ranges from 0.23 to 0.55), %HI of 15.13 and z-score of 2.27. The authors presume that haploinsufficiency may not apply, and consider a gain-of-function/dominant-negative effect more likely. As the authors comment LMBRD2 (LMBR1 domain containing 2) encodes a membrane bound protein with poorly described function. It is widely expressed across tissues with notable expression in human brain (also in Drosophila, or Xenopus laevis). It displays high interspecies conservation. It has been suggested (Paek et al - PMID: 28388415) that LMBRD2 is a potential regulator of β2 adrenoreceptor signalling through involvement in GPCR signalling. ► Kaplanis et al (2020 - https://doi.org/10.1101/797787) in a dataset of 31058 parent-offspring trios (WES) previously identified 3 individuals with developmental disorder, harboring c.1448G>A - p.Arg483His. These individuals (1 from the DDD study, and 2 GeneDx patients) appear in Decipher. [ https://decipher.sanger.ac.uk/ddd/research-variant/40e17c78cc9655a6721006fc1e0c98db/overview ]. The preprint by Kaplanis et al is cited by Malhotra et al, with Arg483His reported in 6 patients overall in both studies. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | SPOP |
Arina Puzriakova changed review comment from: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. Associated with Nabais Sa-de Vries syndrome in OMIM, and a probable gene for SPOP-related Neurodevelopmental Disorder in G2P. At least 7 unrelated individuals with mild-severe ID, associated with de novo missense variants in the SPOP gene. Additional variable features include craniofacial dysmorphisms, cardiovascular abnormalities, hearing impairment, and endocrine abnormalities. Functional studies show differing effects of the variants (gain-of-function or dominant-negative) that correspond to the different clinical manifestations.; to: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. Associated with Nabais Sa-de Vries syndrome in OMIM, and a probable gene for SPOP-related Neurodevelopmental Disorder in G2P. At least 7 unrelated individuals with mild-severe ID, associated with de novo missense variants in the SPOP gene. Additional variable features include craniofacial dysmorphisms, cardiovascular abnormalities, hearing impairment, and endocrine abnormalities. Functional studies show differing effects of the variants (gain-of-function or dominant-negative) that correspond to differences in additional clinical manifestations. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | TASP1 | Arina Puzriakova Tag for-review tag was added to gene: TASP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | TASP1 | Arina Puzriakova Classified gene: TASP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | TASP1 |
Arina Puzriakova Added comment: Comment on list classification: Sufficient cases for a GREEN rating at the next major review. Associated with phenotype in OMIM, and a possible gene for Developmental delay, happy demeanor, distinctive facial features, and congenital anomalies in G2P. Four unrelated patients with homozygous LOF variants in this gene all exhibited a consistent phenotype which included global developmental delay. All variants segregated with disease, but no functional studies of the variants or patient cells were not performed. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.262 | TASP1 | Arina Puzriakova Gene: tasp1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.261 | SPOP | Arina Puzriakova Phenotypes for gene: SPOP were changed from Intellectual disability; dysmorphism; microcephaly; macrocephaly to Nabais Sa-de Vries syndrome, type 1, 618828; Nabais Sa-de Vries syndrome, type 2, 618829 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.260 | SPOP | Arina Puzriakova Tag for-review tag was added to gene: SPOP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.260 | SPOP | Arina Puzriakova Classified gene: SPOP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.260 | SPOP |
Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. Associated with Nabais Sa-de Vries syndrome in OMIM, and a probable gene for SPOP-related Neurodevelopmental Disorder in G2P. At least 7 unrelated individuals with mild-severe ID, associated with de novo missense variants in the SPOP gene. Additional variable features include craniofacial dysmorphisms, cardiovascular abnormalities, hearing impairment, and endocrine abnormalities. Functional studies show differing effects of the variants (gain-of-function or dominant-negative) that correspond to the different clinical manifestations. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.260 | SPOP | Arina Puzriakova Gene: spop has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.259 | POMK | Arina Puzriakova Publications for gene: POMK were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.258 | POMK | Arina Puzriakova Classified gene: POMK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.258 | POMK |
Arina Puzriakova Added comment: Comment on list classification: Sufficient cases to support causation; however, ID is unlikely to be the main presenting feature of this phenotype - therefore, rating Amber on this panel. POMK is rated Green on other relevant panels including Congenital muscular dystrophy, Hydrocephalus, and Arthrogryposis. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.258 | POMK | Arina Puzriakova Gene: pomk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.257 | PISD | Arina Puzriakova Classified gene: PISD as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.257 | PISD | Arina Puzriakova Added comment: Comment on list classification: Four families presenting a DD/ID phenotype, but three share the same founder variant - Rating Amber until further cases are reported (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.257 | PISD | Arina Puzriakova Gene: pisd has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.256 | PISD | Arina Puzriakova Tag watchlist tag was added to gene: PISD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.256 | PISD | Arina Puzriakova reviewed gene: PISD: Rating: ; Mode of pathogenicity: None; Publications: 31263216, 30858161, 30488656, 3561949; Phenotypes: Liberfarb syndrome, 618889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.256 | PIBF1 | Arina Puzriakova Tag for-review tag was added to gene: PIBF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.256 | PIBF1 | Arina Puzriakova Classified gene: PIBF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.256 | PIBF1 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - at least 7 families (4 with same founder variant) with Joubert syndrome, which is associated with global DD/ID. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.256 | PIBF1 | Arina Puzriakova Gene: pibf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | PIBF1 | Arina Puzriakova reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26167768, 29695797, 30858804; Phenotypes: Joubert syndrome 33, 617767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | TAF1C |
Konstantinos Varvagiannis gene: TAF1C was added gene: TAF1C was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TAF1C were set to 32779182 Phenotypes for gene: TAF1C were set to Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology Penetrance for gene: TAF1C were set to Complete Review for gene: TAF1C was set to AMBER Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual). Following a normal CMA, exome in the first case revealed a homozygous missense SNV (NM_005679.3:c.1165C>T / p.Arg389Cys) supported by in silico predictions. mRNA and protein levels were substantially reduced in fibroblasts from this subject. Only the patient and parents were tested for the variant but not 3 unaffected sibs (fig1). The second individual was homozygous for another missense variant (p.Arg405Cys) also supported by in silico predictions. The girl was the single affected person within the family with an unaffected sib and parents heterozygous for the variant. Several other unaffected relatives in the extended pedigree were either carriers for this variant or homozygous for the wt allele. TAF1C encodes the TATA-box binding protein associated factor (TAF) RNA polymerase I subunit. RNA polymerase I (Pol I) transcribes genes to produce rRNA. For Pol I to initiate transcription, two transcription factors are required : UBF (upstream binding factor encoded by UBTF) and SL1 (selectivity factor 1). The latter is formed by TBP (TATA-binding protein) and 3 Pol I-specific TBP-associated factors (TAFs). A recurrent de novo missense variant in UBTF (encoding the other Pol I transcription factor) causes a disorder with highly similar features. The specific variant acts through a gain-of-function mechanism (and not by LoF which appears to apply for TAF1C based on expression data). The authors hypothesize that altered Pol I activity and resulting ribosomal stress could cause the microcephaly and leukodystrophy (both reported in 1 - the same - individual). As a result, TAF1C may be considered for inclusion in the ID panel with amber rating pending further evidence. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | ZMPSTE24 | Arina Puzriakova commented on gene: ZMPSTE24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | ZIC3 | Arina Puzriakova commented on gene: ZIC3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | XPC | Arina Puzriakova commented on gene: XPC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | WRAP53 | Arina Puzriakova commented on gene: WRAP53 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | WNT7A | Arina Puzriakova commented on gene: WNT7A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | WNT3 | Arina Puzriakova commented on gene: WNT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | WNT10B | Arina Puzriakova commented on gene: WNT10B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.255 | WDR35 | Arina Puzriakova commented on gene: WDR35 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | WDR34 | Arina Puzriakova commented on gene: WDR34 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | WDR19 | Arina Puzriakova commented on gene: WDR19 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | VSX2 | Arina Puzriakova commented on gene: VSX2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | UVSSA | Arina Puzriakova commented on gene: UVSSA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | USB1 | Arina Puzriakova commented on gene: USB1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | UROS | Arina Puzriakova commented on gene: UROS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | UGT1A1 | Arina Puzriakova commented on gene: UGT1A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TYRP1 | Arina Puzriakova commented on gene: TYRP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TYR | Arina Puzriakova commented on gene: TYR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TXNL4A | Arina Puzriakova commented on gene: TXNL4A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TUBA8 | Arina Puzriakova commented on gene: TUBA8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TSHR | Arina Puzriakova commented on gene: TSHR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TRPV4 | Arina Puzriakova commented on gene: TRPV4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TRPS1 | Arina Puzriakova commented on gene: TRPS1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TRPM1 | Arina Puzriakova commented on gene: TRPM1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TRIP11 | Arina Puzriakova commented on gene: TRIP11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TRAPPC2 | Arina Puzriakova commented on gene: TRAPPC2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TP63 | Arina Puzriakova commented on gene: TP63 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TMPRSS6 | Arina Puzriakova commented on gene: TMPRSS6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TMEM126B | Arina Puzriakova commented on gene: TMEM126B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TGFB3 | Arina Puzriakova commented on gene: TGFB3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TGFB2 | Arina Puzriakova commented on gene: TGFB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TEK | Arina Puzriakova commented on gene: TEK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TCF12 | Arina Puzriakova commented on gene: TCF12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBXAS1 | Arina Puzriakova commented on gene: TBXAS1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBX5 | Arina Puzriakova commented on gene: TBX5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBX4 | Arina Puzriakova commented on gene: TBX4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBX3 | Arina Puzriakova commented on gene: TBX3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBX22 | Arina Puzriakova commented on gene: TBX22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBX20 | Arina Puzriakova commented on gene: TBX20 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TBX15 | Arina Puzriakova commented on gene: TBX15 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | TAB2 | Arina Puzriakova commented on gene: TAB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | STS | Arina Puzriakova commented on gene: STS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | STAT1 | Arina Puzriakova commented on gene: STAT1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | STAR | Arina Puzriakova commented on gene: STAR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | SRY | Arina Puzriakova commented on gene: SRY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | SPEG | Arina Puzriakova commented on gene: SPEG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | SPAG1 | Arina Puzriakova commented on gene: SPAG1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | SOX17 | Arina Puzriakova commented on gene: SOX17 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | SMCHD1 | Arina Puzriakova commented on gene: SMCHD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | SCN4A | Arina Puzriakova commented on gene: SCN4A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RUNX2 | Arina Puzriakova commented on gene: RUNX2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RSPO4 | Arina Puzriakova commented on gene: RSPO4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RSPH3 | Arina Puzriakova commented on gene: RSPH3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RSPH1 | Arina Puzriakova commented on gene: RSPH1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RPS19 | Arina Puzriakova commented on gene: RPS19 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RPGRIP1 | Arina Puzriakova commented on gene: RPGRIP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RPE65 | Arina Puzriakova commented on gene: RPE65 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | ROBO3 | Arina Puzriakova commented on gene: ROBO3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.254 | RETREG1 | Arina Puzriakova commented on gene: RETREG1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | RASA1 | Arina Puzriakova commented on gene: RASA1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | PGM1 | Arina Puzriakova commented on gene: PGM1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | PDE6G | Arina Puzriakova commented on gene: PDE6G | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | PAX9 | Arina Puzriakova commented on gene: PAX9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | PAX3 | Arina Puzriakova commented on gene: PAX3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | PAPSS2 | Arina Puzriakova commented on gene: PAPSS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | OTULIN | Arina Puzriakova commented on gene: OTULIN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | OTOGL | Arina Puzriakova commented on gene: OTOGL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | ORC6 | Arina Puzriakova commented on gene: ORC6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NRXN2 | Arina Puzriakova commented on gene: NRXN2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NR5A1 | Arina Puzriakova commented on gene: NR5A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NR2F2 | Arina Puzriakova commented on gene: NR2F2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NPR2 | Arina Puzriakova commented on gene: NPR2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NPHS1 | Arina Puzriakova commented on gene: NPHS1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NPHP4 | Arina Puzriakova commented on gene: NPHP4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NOTCH2 | Arina Puzriakova commented on gene: NOTCH2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NOG | Arina Puzriakova commented on gene: NOG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NODAL | Arina Puzriakova commented on gene: NODAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NMNAT1 | Arina Puzriakova commented on gene: NMNAT1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NKX3-2 | Arina Puzriakova commented on gene: NKX3-2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | NEK1 | Arina Puzriakova commented on gene: NEK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MYO5B | Arina Puzriakova commented on gene: MYO5B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MYH9 | Arina Puzriakova commented on gene: MYH9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MYH8 | Arina Puzriakova commented on gene: MYH8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MYH6 | Arina Puzriakova commented on gene: MYH6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MSX2 | Arina Puzriakova commented on gene: MSX2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MSX1 | Arina Puzriakova commented on gene: MSX1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MNX1 | Arina Puzriakova commented on gene: MNX1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MMP13 | Arina Puzriakova commented on gene: MMP13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MFRP | Arina Puzriakova commented on gene: MFRP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MESP2 | Arina Puzriakova commented on gene: MESP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MC2R | Arina Puzriakova commented on gene: MC2R | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MATN3 | Arina Puzriakova commented on gene: MATN3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MAPK10 | Arina Puzriakova commented on gene: MAPK10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | MAP3K1 | Arina Puzriakova commented on gene: MAP3K1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LTBP3 | Arina Puzriakova commented on gene: LTBP3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LTBP2 | Arina Puzriakova commented on gene: LTBP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LRRC6 | Arina Puzriakova commented on gene: LRRC6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LRP4 | Arina Puzriakova commented on gene: LRP4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LMX1B | Arina Puzriakova commented on gene: LMX1B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LMNA | Arina Puzriakova commented on gene: LMNA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LHX4 | Arina Puzriakova commented on gene: LHX4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LHX3 | Arina Puzriakova commented on gene: LHX3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LFNG | Arina Puzriakova commented on gene: LFNG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LEMD3 | Arina Puzriakova commented on gene: LEMD3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | LDB3 | Arina Puzriakova commented on gene: LDB3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | KLHL40 | Arina Puzriakova commented on gene: KLHL40 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | KLF1 | Arina Puzriakova commented on gene: KLF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | KIT | Arina Puzriakova commented on gene: KIT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.253 | KIRREL3 | Arina Puzriakova commented on gene: KIRREL3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | KIF22 | Arina Puzriakova commented on gene: KIF22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | KCTD1 | Arina Puzriakova commented on gene: KCTD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | KCNQ1 | Arina Puzriakova commented on gene: KCNQ1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | KCND3 | Arina Puzriakova commented on gene: KCND3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | KBTBD13 | Arina Puzriakova commented on gene: KBTBD13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | JAK3 | Arina Puzriakova commented on gene: JAK3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | JAGN1 | Arina Puzriakova commented on gene: JAGN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | JAG1 | Arina Puzriakova commented on gene: JAG1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IRF6 | Arina Puzriakova commented on gene: IRF6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | INPPL1 | Arina Puzriakova commented on gene: INPPL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IMPAD1 | Arina Puzriakova commented on gene: IMPAD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IL11RA | Arina Puzriakova commented on gene: IL11RA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IHH | Arina Puzriakova commented on gene: IHH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IGF2 | Arina Puzriakova commented on gene: IGF2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IFT80 | Arina Puzriakova commented on gene: IFT80 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IFT122 | Arina Puzriakova commented on gene: IFT122 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | IFITM5 | Arina Puzriakova commented on gene: IFITM5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HYDIN | Arina Puzriakova commented on gene: HYDIN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HYAL1 | Arina Puzriakova commented on gene: HYAL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HSF4 | Arina Puzriakova commented on gene: HSF4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HSD3B7 | Arina Puzriakova commented on gene: HSD3B7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HR | Arina Puzriakova commented on gene: HR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HPSE2 | Arina Puzriakova commented on gene: HPSE2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HPS1 | Arina Puzriakova commented on gene: HPS1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HPGD | Arina Puzriakova commented on gene: HPGD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HOXD13 | Arina Puzriakova commented on gene: HOXD13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HOXC13 | Arina Puzriakova commented on gene: HOXC13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HOXA13 | Arina Puzriakova commented on gene: HOXA13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HNF4A | Arina Puzriakova commented on gene: HNF4A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | HMGCS2 | Arina Puzriakova commented on gene: HMGCS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GUCY2C | Arina Puzriakova commented on gene: GUCY2C | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GRM6 | Arina Puzriakova commented on gene: GRM6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GRHL3 | Arina Puzriakova commented on gene: GRHL3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GPR179 | Arina Puzriakova commented on gene: GPR179 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GNAI3 | Arina Puzriakova commented on gene: GNAI3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GLMN | Arina Puzriakova commented on gene: GLMN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GLE1 | Arina Puzriakova commented on gene: GLE1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GJB1 | Arina Puzriakova commented on gene: GJB1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GJA8 | Arina Puzriakova commented on gene: GJA8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GJA3 | Arina Puzriakova commented on gene: GJA3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GJA1 | Arina Puzriakova commented on gene: GJA1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GHR | Arina Puzriakova commented on gene: GHR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GDF6 | Arina Puzriakova commented on gene: GDF6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GDF5 | Arina Puzriakova commented on gene: GDF5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GBA2 | Arina Puzriakova commented on gene: GBA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GATA4 | Arina Puzriakova commented on gene: GATA4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GATA2 | Arina Puzriakova commented on gene: GATA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GAS8 | Arina Puzriakova commented on gene: GAS8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GALK1 | Arina Puzriakova commented on gene: GALK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.252 | GAA | Arina Puzriakova commented on gene: GAA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FZD6 | Arina Puzriakova commented on gene: FZD6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FYCO1 | Arina Puzriakova commented on gene: FYCO1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FXN | Arina Puzriakova commented on gene: FXN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FTL | Arina Puzriakova commented on gene: FTL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FOXN1 | Arina Puzriakova commented on gene: FOXN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FOXF1 | Arina Puzriakova commented on gene: FOXF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FOXE3 | Arina Puzriakova commented on gene: FOXE3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FOXE1 | Arina Puzriakova commented on gene: FOXE1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FOXC2 | Arina Puzriakova commented on gene: FOXC2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FOXC1 | Arina Puzriakova commented on gene: FOXC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FLT4 | Arina Puzriakova commented on gene: FLT4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FLNB | Arina Puzriakova commented on gene: FLNB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FKBP14 | Arina Puzriakova commented on gene: FKBP14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FHL1 | Arina Puzriakova commented on gene: FHL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FGF3 | Arina Puzriakova commented on gene: FGF3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FGF10 | Arina Puzriakova commented on gene: FGF10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FBXW4 | Arina Puzriakova commented on gene: FBXW4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FBP1 | Arina Puzriakova commented on gene: FBP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FBN1 | Arina Puzriakova commented on gene: FBN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FAM20A | Arina Puzriakova commented on gene: FAM20A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FAM161A | Arina Puzriakova commented on gene: FAM161A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | FAAH2 | Arina Puzriakova commented on gene: FAAH2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | EYA1 | Arina Puzriakova commented on gene: EYA1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | EVC2 | Arina Puzriakova commented on gene: EVC2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | EVC | Arina Puzriakova commented on gene: EVC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | ERMARD | Arina Puzriakova commented on gene: ERMARD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | ERF | Arina Puzriakova commented on gene: ERF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | ERCC4 | Arina Puzriakova commented on gene: ERCC4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | EOGT | Arina Puzriakova commented on gene: EOGT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | ENPP1 | Arina Puzriakova commented on gene: ENPP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | ELN | Arina Puzriakova commented on gene: ELN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | EDNRA | Arina Puzriakova commented on gene: EDNRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | EDA | Arina Puzriakova commented on gene: EDA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | ECEL1 | Arina Puzriakova commented on gene: ECEL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DYNC2H1 | Arina Puzriakova commented on gene: DYNC2H1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DVL1 | Arina Puzriakova commented on gene: DVL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DSTYK | Arina Puzriakova commented on gene: DSTYK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DSPP | Arina Puzriakova commented on gene: DSPP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DPM3 | Arina Puzriakova commented on gene: DPM3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DNAAF4 | Arina Puzriakova commented on gene: DNAAF4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DNAAF3 | Arina Puzriakova commented on gene: DNAAF3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DMP1 | Arina Puzriakova commented on gene: DMP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DLL4 | Arina Puzriakova commented on gene: DLL4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DLL3 | Arina Puzriakova commented on gene: DLL3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DDB2 | Arina Puzriakova commented on gene: DDB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | DCC | Arina Puzriakova commented on gene: DCC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | CYP7B1 | Arina Puzriakova commented on gene: CYP7B1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | CYP1B1 | Arina Puzriakova commented on gene: CYP1B1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | CTSK | Arina Puzriakova commented on gene: CTSK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.251 | CTSF | Arina Puzriakova commented on gene: CTSF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CTNS | Arina Puzriakova commented on gene: CTNS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRYGD | Arina Puzriakova commented on gene: CRYGD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRYBB3 | Arina Puzriakova commented on gene: CRYBB3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRYBB2 | Arina Puzriakova commented on gene: CRYBB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRYBB1 | Arina Puzriakova commented on gene: CRYBB1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRYBA1 | Arina Puzriakova commented on gene: CRYBA1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRYAA | Arina Puzriakova commented on gene: CRYAA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRX | Arina Puzriakova commented on gene: CRX | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CRB1 | Arina Puzriakova commented on gene: CRB1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COMP | Arina Puzriakova commented on gene: COMP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL9A3 | Arina Puzriakova commented on gene: COL9A3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL9A2 | Arina Puzriakova commented on gene: COL9A2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL9A1 | Arina Puzriakova commented on gene: COL9A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL6A1 | Arina Puzriakova commented on gene: COL6A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL4A4 | Arina Puzriakova commented on gene: COL4A4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL4A3 | Arina Puzriakova commented on gene: COL4A3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL2A1 | Arina Puzriakova commented on gene: COL2A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL1A1 | Arina Puzriakova commented on gene: COL1A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL18A1 | Arina Puzriakova commented on gene: COL18A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL11A1 | Arina Puzriakova commented on gene: COL11A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | COL10A1 | Arina Puzriakova commented on gene: COL10A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CLDN19 | Arina Puzriakova commented on gene: CLDN19 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CLCN7 | Arina Puzriakova commented on gene: CLCN7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CIB2 | Arina Puzriakova commented on gene: CIB2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CHUK | Arina Puzriakova commented on gene: CHUK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CHSY1 | Arina Puzriakova commented on gene: CHSY1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CHST3 | Arina Puzriakova commented on gene: CHST3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CHRNG | Arina Puzriakova commented on gene: CHRNG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CHRDL1 | Arina Puzriakova commented on gene: CHRDL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CHM | Arina Puzriakova commented on gene: CHM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CDH3 | Arina Puzriakova commented on gene: CDH3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CDH23 | Arina Puzriakova commented on gene: CDH23 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CCT5 | Arina Puzriakova commented on gene: CCT5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CCNO | Arina Puzriakova commented on gene: CCNO | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CCDC65 | Arina Puzriakova commented on gene: CCDC65 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CCDC40 | Arina Puzriakova commented on gene: CCDC40 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CCDC114 | Arina Puzriakova commented on gene: CCDC114 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | CCDC103 | Arina Puzriakova commented on gene: CCDC103 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | C4orf26 | Arina Puzriakova commented on gene: C4orf26 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | C2orf71 | Arina Puzriakova commented on gene: C2orf71 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | C19orf12 | Arina Puzriakova commented on gene: C19orf12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | BMPR1B | Arina Puzriakova commented on gene: BMPR1B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | BMPER | Arina Puzriakova commented on gene: BMPER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | BICD2 | Arina Puzriakova commented on gene: BICD2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | BHLHA9 | Arina Puzriakova commented on gene: BHLHA9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | BGN | Arina Puzriakova commented on gene: BGN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | BFSP2 | Arina Puzriakova commented on gene: BFSP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | ATP8B1 | Arina Puzriakova commented on gene: ATP8B1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | ATP6V1B1 | Arina Puzriakova commented on gene: ATP6V1B1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.250 | ARHGEF6 | Arina Puzriakova commented on gene: ARHGEF6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.249 | ALDOB | Arina Puzriakova commented on gene: ALDOB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.249 | AGL | Arina Puzriakova commented on gene: AGL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.249 | ADGRG6 | Arina Puzriakova commented on gene: ADGRG6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.249 | ADCY5 | Arina Puzriakova commented on gene: ADCY5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.249 | ABCC6 | Arina Puzriakova commented on gene: ABCC6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.248 | ACOX2 | Arina Puzriakova Classified gene: ACOX2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.248 | ACOX2 | Arina Puzriakova Added comment: Comment on list classification: Rating Red - to date, only mild ID reported in a single patient. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.248 | ACOX2 | Arina Puzriakova Gene: acox2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.247 | PDP1 | Arina Puzriakova Classified gene: PDP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.247 | PDP1 | Arina Puzriakova Added comment: Comment on list classification: Rating Amber, given the mild delay in psychomotor development seen in these patients. This gene is Green on other panels which are more relevant to the phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.247 | PDP1 | Arina Puzriakova Gene: pdp1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.246 | PDP1 | Arina Puzriakova reviewed gene: PDP1: Rating: ; Mode of pathogenicity: None; Publications: 15855260, 19184109, 31392110; Phenotypes: Pyruvate dehydrogenase phosphatase deficiency, 608782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.246 | PNPT1 | Arina Puzriakova Tag for-review tag was added to gene: PNPT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.246 | PDHB | Arina Puzriakova Publications for gene: PDHB were set to 15138885; 26014431 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.245 | PDHB | Arina Puzriakova Classified gene: PDHB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.245 | PDHB | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - moderate ID/DD reported in multiple surviving patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.245 | PDHB | Arina Puzriakova Gene: pdhb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | PDHB | Arina Puzriakova Tag for-review tag was added to gene: PDHB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | CNTNAP1 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported four unrelated cases of Lethal congenital contracture syndrome 7 616286 and seven variants reported in four cases of Hypomyelinating neuropathy, congenital, 3 618186. Both of these conditions include intellectual disability.; to: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Lethal congenital contracture syndrome 7 61628. At least four variants reported four unrelated cases of Lethal congenital contracture syndrome 7 616286 and seven variants reported in four cases of Hypomyelinating neuropathy, congenital, 3 618186. Both of these conditions include intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | B9D2 | Sarah Leigh commented on gene: B9D2: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | CNTNAP1 | Sarah Leigh edited their review of gene: CNTNAP1: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | CNTNAP1 | Sarah Leigh Classified gene: CNTNAP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | CNTNAP1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported four unrelated cases of Lethal congenital contracture syndrome 7 616286 and seven variants reported in four cases of Hypomyelinating neuropathy, congenital, 3 618186. Both of these conditions include intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.244 | CNTNAP1 | Sarah Leigh Gene: cntnap1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.243 | CNTNAP1 | Sarah Leigh Tag for-review tag was added to gene: CNTNAP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.243 | CNTNAP1 | Sarah Leigh Phenotypes for gene: CNTNAP1 were changed from Hypomyelinating neuropathy, congenital, 3, MIM#618186; Lethal congenital contracture syndrome 7, MIM# 616286 to Hypomyelinating neuropathy, congenital, 3 618186; Lethal congenital contracture syndrome 7 616286 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.242 | B9D2 | Sarah Leigh edited their review of gene: B9D2: Added comment: Three variants were reported in two unrelated cases of Joubert syndrome 34, which includes intellectual impairment, together with supportive functional studies (PMID 21763481).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.242 | B9D2 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.242 | B9D2 | Sarah Leigh Classified gene: B9D2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.242 | B9D2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in four unrelated cases. Three of the variants were reported in two unrelated cases of Joubert syndrome 34, which includes intellectual impairment and the remaining three variants were found in two unrelated fetuses with Meckel syndrome 10, with brain malformations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.242 | B9D2 | Sarah Leigh Gene: b9d2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.241 | B9D2 | Sarah Leigh Tag for-review tag was added to gene: B9D2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.241 | B9D2 | Sarah Leigh Phenotypes for gene: B9D2 were changed from Joubert syndrome 34, MIM#614175; Meckel syndrome 10, MIM#614175 to Joubert syndrome 34 614175; Meckel syndrome 10 614175 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.241 | B9D2 | Sarah Leigh Classified gene: B9D2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.241 | B9D2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in four unrelated cases. Three of the variants were reported in two unrelated cases of Joubert syndrome 34, which includes intellectual impairment and the remaining three variants were found in two unrelated fetuses with Meckel syndrome 10, with brain malformations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.241 | B9D2 | Sarah Leigh Gene: b9d2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.240 | B9D2 | Sarah Leigh Publications for gene: B9D2 were set to 26092869; 21763481 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | MADD | Konstantinos Varvagiannis reviewed gene: MADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 29302074, 32761064; Phenotypes: Global developmental delay / Intellectual disability / Seizures, Global developmental delay / Intellectual disability / Seizures / Abnormality of the endocrine system / Exocrine pancreatic insufficiency / Constipation / Diarrhea / Anemia / Thrombocytopenia / Abnormality of the autonomic nervous system; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | FAM50A |
Konstantinos Varvagiannis gene: FAM50A was added gene: FAM50A was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FAM50A 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: FAM50A were set to 32703943 Phenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261) Penetrance for gene: FAM50A were set to unknown Review for gene: FAM50A was set to GREEN Added comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.). Please consider inclusion in the ID panel with green rating and epilepsy panel with amber (seizures in individuals from 2 families). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | TET3 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype including mild to severe intellectual disability in OMIM and as probable Gen2Phen gene for TET3 DNA Demethylation Disorder biallelic and TET3 DNA Demethylation Disorder monoallelic. At least 9 variants reported in total, with 5 variants associated with the biallelic version of the condition in 3 unrelated cases and 4 variants associated with the monoallelic version in 4 unrelated cases.; to: Comment on list classification: Associated with relevant phenotype OMIM and as probable Gen2Phen gene for TET3 DNA Demethylation Disorder biallelic and TET3 DNA Demethylation Disorder monoallelic. At least 9 variants reported in total, with 5 variants associated with the biallelic version of the condition in 3 unrelated cases and 4 variants associated with the monoallelic version in 4 unrelated cases. Mild to severe intellectual disability was reported in 2 unrelated cases of monoallelic and 2 unrelated cases of biallelic 2 cases TET3 DNA Demethylation Disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | TET3 | Sarah Leigh commented on gene: TET3: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | TET3 | Sarah Leigh Classified gene: TET3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | TET3 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype including mild to severe intellectual disability in OMIM and as probable Gen2Phen gene for TET3 DNA Demethylation Disorder biallelic and TET3 DNA Demethylation Disorder monoallelic. At least 9 variants reported in total, with 5 variants associated with the biallelic version of the condition in 3 unrelated cases and 4 variants associated with the monoallelic version in 4 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | TET3 | Sarah Leigh Gene: tet3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.239 | TET3 | Sarah Leigh Publications for gene: TET3 were set to https://doi.org/10.1016/j.ajhg.2019.12.007 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.238 | TET3 | Sarah Leigh Tag for-review tag was added to gene: TET3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.238 | TET3 | Sarah Leigh Added comment: Comment on phenotypes: This recognized as TET3 DNA Demethylation Disorder biallelic and TET3 DNA Demethylation Disorder monoallelic in Gen2Phen (https://www.ebi.ac.uk/gene2phenotype/search?panel=ALL&search_term=TET3#). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.238 | TET3 | Sarah Leigh Phenotypes for gene: TET3 were changed from Global developmental delay; Intellectual disability; Macrocephaly; Growth abnormality; Seizures; Autistic behavior; Abnormality of movement; Abnormality of the face to Beck-Fahrner syndrome 618798 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.237 | AFF3 | Sarah Leigh reviewed gene: AFF3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.237 | AFF3 | Sarah Leigh Publications for gene: AFF3 were set to https://doi.org/10.1101/693937; 18616733 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.236 | SUZ12 | Sarah Leigh Phenotypes for gene: SUZ12 were changed from Overgrowth; Global developmental delay; Intellectual disability; Accelerated skeletal maturation; Abnormality of the skeletal system; Abnormality of the genitourinary system; Abnormality of the corpus callosum; Abnormality of the respiratory system; Abnormality of the abdominal wall to Imagawa-Matsumoto syndrome 618786 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.235 | SUZ12 | Sarah Leigh Classified gene: SUZ12 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.235 | SUZ12 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in at least 13 affected individuals from 12 families, of whome 7 had mostly mild intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.235 | SUZ12 | Sarah Leigh Gene: suz12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | SUZ12 | Sarah Leigh Tag for-review tag was added to gene: SUZ12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh edited their review of gene: OXR1: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Classified gene: OXR1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction. At least 4 variants reported in at least 3 unrelated cases, who all had epilepsy and global developmental delay. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Gene: oxr1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Tag for-review tag was added to gene: OXR1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Classified gene: OXR1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction. At least 4 variants reported in at least 3 unrelated cases, who all had epilepsy and global developmental delay. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.234 | OXR1 | Sarah Leigh Gene: oxr1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.233 | OXR1 | Sarah Leigh Publications for gene: OXR1 were set to 31785787 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.232 | OXR1 | Sarah Leigh Phenotypes for gene: OXR1 were changed from Central hypotonia; Global developmental delay; Delayed speech and language development; Intellectual disability; Seizures; Abnormality of the cerebellum to Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay 213000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.231 | OXR1 | Sarah Leigh Publications for gene: OXR1 were set to https://doi.org/10.1016/j.ajhg.2019.11.002 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.230 | SFXN4 | Sarah Leigh Classified gene: SFXN4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.230 | SFXN4 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 5 variants reported in at least 3 unreleated cases, with mild to severe intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.230 | SFXN4 | Sarah Leigh Gene: sfxn4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.229 | SFXN4 | Sarah Leigh Tag for-review tag was added to gene: SFXN4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.229 | SFXN4 | Sarah Leigh Phenotypes for gene: SFXN4 were changed from Combined oxidative phosphorylation deficiency 18, MIM#615578 to Combined oxidative phosphorylation deficiency 18 615578 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.228 | MTHFS | Sarah Leigh edited their review of gene: MTHFS: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.228 | MTHFS | Sarah Leigh Tag for-review tag was added to gene: MTHFS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.228 | MTHFS | Sarah Leigh Classified gene: MTHFS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.228 | MTHFS | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 4 variants reported in at least 3 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.228 | MTHFS | Sarah Leigh Gene: mthfs has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.227 | YARS | Sarah Leigh Added comment: Comment on phenotypes: Monoallelic variants are associated with Charcot-Marie-Tooth disease, dominant intermediate C 608323, while biallelic variants are associated with a complex phenotype that may include intellectual disability, hearing loss and liver damage. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.227 | YARS | Sarah Leigh Phenotypes for gene: YARS were changed from Intellectual disability; deafness; nystagmus; liver dysfunction to Charcot-Marie-Tooth disease, dominant intermediate C 608323; Intellectual disability; deafness; nystagmus; liver dysfunction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | YARS | Sarah Leigh Tag watchlist tag was added to gene: YARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | NRROS | Sarah Leigh Tag for-review tag was added to gene: NRROS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | PJA1 | Zornitza Stark reviewed gene: PJA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32530565; Phenotypes: Intellectual disability, trigonocephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | SCAF4 | Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 32730804; Phenotypes: intellectual disability, seizures, behavioral abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | PIGQ | Konstantinos Varvagiannis reviewed gene: PIGQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 32588908, 24463883, 25558065, 31148362; Phenotypes: Epileptic encephalopathy, early infantile, 77 (MIM #618548); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | EIF2AK2 | Arina Puzriakova Classified gene: EIF2AK2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | EIF2AK2 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.226 | EIF2AK2 | Arina Puzriakova Gene: eif2ak2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.225 | EIF2AK2 | Arina Puzriakova Tag for-review tag was added to gene: EIF2AK2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.225 | EIF2AK2 | Arina Puzriakova reviewed gene: EIF2AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32197074; Phenotypes: Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, 618877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.225 | FARSB | Arina Puzriakova Classified gene: FARSB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.225 | FARSB | Arina Puzriakova Added comment: Comment on list classification: Rating Amber following consultation with the clinical team in view of the inconsistent phenotype. Patients are more likely to be recognised on the basis of other phenotypic features, for which FARSB has been rated Green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.225 | FARSB | Arina Puzriakova Gene: farsb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.224 | FARSB | Arina Puzriakova reviewed gene: FARSB: Rating: AMBER; Mode of pathogenicity: None; Publications: 29573043, 29979980, 30014610; Phenotypes: Rajab interstitial lung disease with brain calcifications, 613658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.224 | IREB2 | Arina Puzriakova Tag watchlist tag was added to gene: IREB2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.224 | IREB2 | Arina Puzriakova Classified gene: IREB2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.224 | IREB2 | Arina Puzriakova Added comment: Comment on list classification: Phenotype is appropriate for this panel, but additional cases necessary to support causation. Therefore rated Amber, awaiting further publications/clinical evidence (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.224 | IREB2 | Arina Puzriakova Gene: ireb2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.223 | IREB2 | Arina Puzriakova reviewed gene: IREB2: Rating: ; Mode of pathogenicity: None; Publications: 30915432, 31243445; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.223 | CHD1 |
Arina Puzriakova changed review comment from: Gene is associated with Pilarowski-Bjornsson syndrome in OMIM, but not in G2P. Pilarowski et al (2018) (PMID: 28866611) reported heterozygous missense variants in five individuals (two sibs and three singletons) as the cause of developmental delay, speech apraxia, hypotonia, and facial dysmorphic features. Two variants were confirmed de novo, while segregation for others could not be determined (including the two sibs who were conceived by egg donor). Developmental delay was noted for all participants; however, ID was only reported in the two sibs.; to: Gene is associated with Pilarowski-Bjornsson syndrome in OMIM, but not in G2P. Pilarowski et al (2018) (PMID: 28866611) reported heterozygous missense variants in five individuals (two sibs and three singletons) as the cause of developmental delay, speech apraxia, hypotonia, and facial dysmorphic features. Two variants were confirmed de novo, while segregation for others could not be determined (including the two sibs who were conceived by egg donor). Developmental delay was noted for all participants; however, ID was only reported in the two sibs. Further insight may be gained from re-evaluation of the two patients in the present study who were too young for a formal neurocognitive evaluation at the time of publication. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.223 | CHD1 | Arina Puzriakova Classified gene: CHD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.223 | CHD1 | Arina Puzriakova Added comment: Comment on list classification: Phenotype is appropriate for the panel, but insufficient cases to support causation (ID only reported in two sibs). Therefore rated Amber, awaiting further publications/clinical evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.223 | CHD1 | Arina Puzriakova Gene: chd1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.222 | CHD1 | Arina Puzriakova reviewed gene: CHD1: Rating: ; Mode of pathogenicity: None; Publications: 28866611; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.222 | PAM16 | Arina Puzriakova Tag founder-effect tag was added to gene: PAM16. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.222 | PAM16 | Arina Puzriakova Classified gene: PAM16 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.222 | PAM16 | Arina Puzriakova Added comment: Comment on list classification: Three unrelated cases, but two share the same founder mutation - Rating Amber until further cases are reported (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.222 | PAM16 | Arina Puzriakova Gene: pam16 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.221 | PAM16 | Arina Puzriakova Tag watchlist tag was added to gene: PAM16. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.221 | PAM16 | Arina Puzriakova reviewed gene: PAM16: Rating: ; Mode of pathogenicity: None; Publications: 24786642, 27354339; Phenotypes: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, 613320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.221 | NDUFA2 | Arina Puzriakova Classified gene: NDUFA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.221 | NDUFA2 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - at least four unrelated cases reported with DD/ID, mostly following a period of regression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.221 | NDUFA2 | Arina Puzriakova Gene: ndufa2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.220 | NDUFA2 |
Arina Puzriakova Tag watchlist was removed from gene: NDUFA2. Tag for-review tag was added to gene: NDUFA2. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.220 | NDUFA2 | Arina Puzriakova Tag watchlist tag was added to gene: NDUFA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.220 | NDUFA2 | Arina Puzriakova reviewed gene: NDUFA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18513682, 28857146, 32154054; Phenotypes: Mitochondrial complex I deficiency, nuclear type 13, 618235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.220 | NDUFAF1 | Arina Puzriakova Classified gene: NDUFAF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.220 | NDUFAF1 | Arina Puzriakova Added comment: Comment on list classification: Additional case of ID required before inclusion of NDUFAF1 on a diagnostic panel (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.220 | NDUFAF1 | Arina Puzriakova Gene: ndufaf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NDUFAF1 | Arina Puzriakova Tag watchlist tag was added to gene: NDUFAF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NDUFAF1 | Arina Puzriakova reviewed gene: NDUFAF1: Rating: ; Mode of pathogenicity: None; Publications: 17557076, 21931170, 24963768; Phenotypes: Mitochondrial complex I deficiency, nuclear type 11, 618234; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NARS |
Konstantinos Varvagiannis changed review comment from: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). As also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. Sources: Literature; to: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). As also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NARS |
Konstantinos Varvagiannis gene: NARS was added gene: NARS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NARS were set to 32738225 Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy Penetrance for gene: NARS were set to Complete Review for gene: NARS was set to GREEN Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). As also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | ZNF407 |
Konstantinos Varvagiannis gene: ZNF407 was added gene: ZNF407 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ZNF407 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ZNF407 were set to 24907849; 32737394; 23195952 Phenotypes for gene: ZNF407 were set to Global developmental delay; Intellectual disability Penetrance for gene: ZNF407 were set to unknown Review for gene: ZNF407 was set to AMBER Added comment: You may consider inclusion of this gene probably with amber rating (or green if the evidence for biallelic variants is considered sufficient). Biallelic variants: - Kambouris et al. (2014 - PMID: 24907849) described 2 brothers with severe DD and ID, born to first cousin parents. Homozygosity mapping, following other non-diagnostic investigations (incl. aCGH), revealed 4 major homozygosity intervals. Exome sequencing in one identified 5 variants within these intervals, ZNF407 (c.5054C>G, p.Ser1685Trp) being the best candidate, supported also by segregation studies. The authors commented that zinc finger proteins act as transcriptional regulators, with mutations in genes encoding for other zinc finger proteins interfering with normal brain development. - Zahra et al. (2020 - PMID: 32737394) report on 7 affected individuals (from 3 families) homozygous or compound heterozygous for ZNF407 variants. Features included hypotonia, DD and ID (in all) and variable occurrence of short stature (6/6), microcephaly (in at least 5), behavioural, visual problems and deafness. Linkage analysis in the first family revealed a 4.4 Mb shared homozygosity region and exome (30x) revealed a 3-bp duplication, confirmed by Sanger sequencing and segregating with the disease (NM_001146189:c.2814_2816dup, p.Val939dup). Affected subjects from the 2 other families were each found to be homozygous (c.2405G>T) or compound heterozygous (c.2884C>G, c.3642G>C) for other variants. Segregation was compatible in all families. Other studies were not performed. The authors comment than only the 3-bp duplication fulfilled ACMG criteria for classification as LP, the other variants being all formally classified as VUS (also due to in silico predictions predicting a LB effect). In addition, while several features such as DD/ID and short stature appeared to be frequent among all patients reported, Zahra et all comment that there was partial clinical overlap with the sibs described by Kambouris et al (additional variants?). Monoallelic disruption of ZNF407: - Ren et al (2013 - PMID: 23195952) described an 8 y.o. boy with ID and ASD. The boy was found to harbor a de novo translocation between chromosomes 3 and 18 [46,XY,t(3;18)(p13;q22.3)]. Array CGH did not reveal any P/LP CNV. Delineation of the breakpoints (FISH, long-range PCR) revealed that the chr18 breakpoint disrupted intron 3 of ZNF407 (isoform 1) with the other breakpoint within a gene-free region of exon 3. There was a loss of 4-8 nt in chr18 and 2-6 in chr3. Sequencing of ZNF407 did not reveal additional variants. RNA isolation in blood followed by RT-PCR studied expression of all 3 ZNF407 isoforms (the intronic region being shared by isoforms 1 and 2). Expression of isoform 1 was shown to be significantly reduced compared to controls. Isoform 2 was undetectable (in blood) while isoform 3 expression was similar to controls. Sequencing of 105 additional patients with similar clinical presentation (ID & ASD) revealed 2 further individuals with de novo missense variants. - Based on the discussion by Kambouris et al (PMID: 24907849 - cited literature not here reviewed) ZNF407 may be deleted in patients with congenital aural atresia due to deletion of a critical region of 18q22.3 (though TSHZ1 is responsible for this phenotype) or 18q- although such deletions span several other genes (cited PMID: 16639285). In one case the breakpoint was shown to be disrupting ZNF407 (cited PMID: 24092497). - The denovo db and Decipher (research variant tab) list few individuals with de novo ZNF407 SNVs although these do not seem to allow conclusions. https://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=ZNF407 https://decipher.sanger.ac.uk/search/ddd-research-variants/results?q=znf407 Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | MAPK1 |
Konstantinos Varvagiannis gene: MAPK1 was added gene: MAPK1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAPK1 were set to 32721402 Phenotypes for gene: MAPK1 were set to Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin Penetrance for gene: MAPK1 were set to unknown Mode of pathogenicity for gene: MAPK1 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: MAPK1 was set to GREEN Added comment: Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants. The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once. MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway. MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic). The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome). The authors comment that screening of 267 additional individuals with suspected RASopathy (without mutations in previously implicated genes) did not reveal other MAPK1 variants. Overall this gene can be considered for inclusion in the ID panel with green rating. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NCAPH | Arina Puzriakova Classified gene: NCAPH as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NCAPH | Arina Puzriakova Added comment: Comment on list classification: Additional cases are required to substantiate causation but added to watchlist. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.219 | NCAPH | Arina Puzriakova Gene: ncaph has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.218 | NCAPH |
Arina Puzriakova gene: NCAPH was added gene: NCAPH was added to Intellectual disability. Sources: Literature watchlist tags were added to gene: NCAPH. Mode of inheritance for gene: NCAPH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCAPH were set to 27737959 Phenotypes for gene: NCAPH were set to Microcephaly 23, primary, autosomal recessive, 617985 Added comment: Associated with Microcephaly 23 in OMIM and a possible gene for microcephaly in G2P. PMID: 27737959 (2016) - A homozygous missense variant in NCAPH (c.728C>T, p.Pro243Leu) was detected in a 42-year-old male with microcephaly (OFC -4.2 SD) and moderate ID. Functional studies indicated that although the variant did not affect cellular protein levels, it disrupted condensin-dependent mitotic chromosome integrity, providing supporting evidence for pathogenicity. Biallelic variants in other genes encoding subunits of the two condensin complexes result in a similar phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.217 | NCAPG2 | Arina Puzriakova Classified gene: NCAPG2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.217 | NCAPG2 | Arina Puzriakova Added comment: Comment on list classification: Additional cases required to ascertain the contribution of NCAPG2 variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.217 | NCAPG2 | Arina Puzriakova Gene: ncapg2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.216 | NCAPG2 | Arina Puzriakova reviewed gene: NCAPG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30609410; Phenotypes: Khan-Khan-Katsanis syndrome, 618460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.216 | NCAPD2 | Arina Puzriakova Tag watchlist tag was added to gene: NCAPD2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.216 | NCAPD2 | Arina Puzriakova Classified gene: NCAPD2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.216 | NCAPD2 | Arina Puzriakova Added comment: Comment on list classification: Amber rating as only one patient has been described with severe ID. However, added to watchlist in case of new reports of more significant cases of ID. Gene has also been added with a Green rating on the Severe Microcephaly panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.216 | NCAPD2 | Arina Puzriakova Gene: ncapd2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.215 | NCAPD2 | Arina Puzriakova reviewed gene: NCAPD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27737959, 28097321, 31056748; Phenotypes: Microcephaly 21, primary, autosomal recessive, 617983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.215 | HADHB | Arina Puzriakova Classified gene: HADHB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.215 | HADHB | Arina Puzriakova Added comment: Comment on list classification: Rating Amber following consultation with the clinical team, in view of the borderline ID phenotype. Cases are more likely to be recognised on the basis of the metabolic phenotype, for which this gene is Green already. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.215 | HADHB | Arina Puzriakova Gene: hadhb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.214 | HADHB | Arina Puzriakova reviewed gene: HADHB: Rating: AMBER; Mode of pathogenicity: None; Publications: 12754706, 19699128; Phenotypes: Trifunctional protein deficiency, 609015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.214 | MN1 | Arina Puzriakova Tag for-review tag was added to gene: MN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.214 | MN1 | Arina Puzriakova Classified gene: MN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.214 | MN1 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.214 | MN1 | Arina Puzriakova Gene: mn1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.213 | VPS51 | Arina Puzriakova Classified gene: VPS51 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.213 | VPS51 | Arina Puzriakova Added comment: Comment on list classification: Additional cases are required before inclusion of VPS51 on a diagnostic panel; however, gene added to watchlist. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.213 | VPS51 | Arina Puzriakova Gene: vps51 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.212 | VPS51 | Arina Puzriakova reviewed gene: VPS51: Rating: AMBER; Mode of pathogenicity: None; Publications: 30624672, 31207318; Phenotypes: Pontocerebellar hypoplasia, type 13, 618606; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.212 | LRRC32 |
Arina Puzriakova changed review comment from: Not associated with phenotype in OMIM or G2P. PMID: 30976112 (2019) - homozygous stop-gain variant in LRRC32 (c.1630C>T; p.Arg544Ter) in three affected individuals from two families with global developmental delay, cleft palate, and proliferative retinopathy. In one family developmental quotient (DQ) varied from borderline low in the female (DQ = 72 at 3 years-2 months) to severely delayed in the male (DQ = 57 at 2 years-11 months). The male in the second family was even more severely delayed (DQ = 23 at 3 years-3 months). Haplotype analysis indicates a founder effect, and therefore further cases are required to substantiate causation.; to: Not associated with phenotype in OMIM or G2P. PMID: 30976112 (2019) - homozygous stop-gain variant in LRRC32 (c.1630C>T; p.Arg544Ter) in three affected individuals from two families with global developmental delay, cleft palate, and proliferative retinopathy. In one family developmental quotient (DQ) varied from borderline low in the female (DQ = 72 at 3 years-2 months) to severely delayed in the male (DQ = 57 at 2 years-11 months). The male in the second family was even more severely delayed (DQ = 23 at 3 years-3 months). Haplotype analysis indicates a founder effect, and therefore further cases are required to substantiate causation (added founder-effect tag). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.212 | LRRC32 | Arina Puzriakova Tag founder-effect tag was added to gene: LRRC32. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.212 | LRRC32 | Arina Puzriakova Classified gene: LRRC32 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.212 | LRRC32 | Arina Puzriakova Added comment: Comment on list classification: Rated Red as there is not currently enough evidence that other variants in the LRRC32 gene are disease causing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.212 | LRRC32 | Arina Puzriakova Gene: lrrc32 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.211 | LRRC32 | Arina Puzriakova reviewed gene: LRRC32: Rating: RED; Mode of pathogenicity: None; Publications: 30976112; Phenotypes: Global developmental delay, Speech delay, Hypotonia, Cleft palate, Proliferative retinopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.211 | LMAN2L | Arina Puzriakova Classified gene: LMAN2L as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.211 | LMAN2L | Arina Puzriakova Added comment: Comment on list classification: Two families with ID phenotype (one mild, one severe). Amber rating as additional cases and functional data are required to validate the causal association with the phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.211 | LMAN2L | Arina Puzriakova Gene: lman2l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.210 | LMAN2L | Arina Puzriakova Tag watchlist tag was added to gene: LMAN2L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.210 | LAMB2 | Arina Puzriakova Classified gene: LAMB2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.210 | LAMB2 | Arina Puzriakova Added comment: Comment on list classification: Given the incomplete penetrance of the ID phenotype, these patients are more likely to be recognised on the basis of the renal phenotype and ocular abnormalilites - LAMB2 has a Green rating on these panels, while an Amber classification might be most appropriate for the ID panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.210 | LAMB2 | Arina Puzriakova Gene: lamb2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | LAMB2 | Arina Puzriakova reviewed gene: LAMB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 15367484, 17256789; Phenotypes: Pierson syndrome, 609049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | TUBB2A | Arina Puzriakova reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32571897; Phenotypes: Cortical dysplasia, complex, with other brain malformations 5, 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | NGLY1 | Eleanor Williams reviewed gene: NGLY1: Rating: ; Mode of pathogenicity: None; Publications: 32259258; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | SETD1B | Arina Puzriakova reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | EEF1A2 | Eleanor Williams changed review comment from: PMID: 32160274 - Davies et al 2020 - several reports of de novo missense mutations in EEF1A2 associated with neurodevelopmental disorders but no clear loss of function mutations. They created mice with a missense mutation in EEF1A2 (D252H) in both heterozygous and homozygous state and EEF1AS null mutant mice and analysed using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. They found the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. The results suggest that the D252H mutation results in a gain of function.; to: PMID: 32160274 - Davies et al 2020 - several reports of de novo missense mutations in EEF1A2 associated with neurodevelopmental disorders but no clear loss of function mutations. They created mice with a missense mutation in EEF1A2 (D252H) in both heterozygous and homozygous state and EEF1A2 null mutant mice and analysed using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. They found the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. The results suggest that the D252H mutation results in a gain of function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | EEF1A2 | Eleanor Williams Tag for-review tag was added to gene: EEF1A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | EEF1A2 | Eleanor Williams reviewed gene: EEF1A2: Rating: ; 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: 32160274; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | HERC2 | Arina Puzriakova Tag for-review tag was added to gene: HERC2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | HERC2 | Arina Puzriakova Classified gene: HERC2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | HERC2 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - more than 3 distinct variants in unrelated cases presenting the relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.209 | HERC2 | Arina Puzriakova Gene: herc2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.208 | IFT27 | Arina Puzriakova Classified gene: IFT27 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.208 | IFT27 | Arina Puzriakova Added comment: Comment on list classification: Given the mild ID phenotype, IFT27 is classified Amber on this panel. Patients are more likely to be recognised in view of other features (e.g. Limb disorders panel), for which this gene is Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.208 | IFT27 | Arina Puzriakova Gene: ift27 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.207 | IFT27 | Arina Puzriakova reviewed gene: IFT27: Rating: AMBER; Mode of pathogenicity: None; Publications: 24488770, 30761183, 29588463; Phenotypes: Bardet-Biedl syndrome 19, 615996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.207 | HNMT | Arina Puzriakova Classified gene: HNMT as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.207 | HNMT | Arina Puzriakova Added comment: Comment on list classification: Amber rating as additional unrelated pedigrees are required before inclusion of HNMT on a diagnostic panel (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.207 | HNMT | Arina Puzriakova Gene: hnmt has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.206 | HNMT | Arina Puzriakova Tag watchlist tag was added to gene: HNMT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.206 | HNMT | Arina Puzriakova reviewed gene: HNMT: Rating: AMBER; Mode of pathogenicity: None; Publications: 26206890; Phenotypes: Intellectual disability, Mental retardation, 616739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.206 | GNE | Arina Puzriakova Classified gene: GNE as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.206 | GNE | Arina Puzriakova Added comment: Comment on list classification: Rating Amber in view of the mild ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.206 | GNE | Arina Puzriakova Gene: gne has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.205 | GNE | Arina Puzriakova reviewed gene: GNE: Rating: AMBER; Mode of pathogenicity: None; Publications: 32053088, 29923088, 10356312, 11326336, 11486897, 27142465; Phenotypes: Sialuria, 269921; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.205 | EXOSC8 | Arina Puzriakova Classified gene: EXOSC8 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.205 | EXOSC8 | Arina Puzriakova Added comment: Comment on list classification: Three unrelated cases, but two share the same founder mutation - Rating Amber until further cases are reported (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.205 | EXOSC8 | Arina Puzriakova Gene: exosc8 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | EXOSC8 |
Arina Puzriakova Tag watchlist tag was added to gene: EXOSC8. Tag founder-effect tag was added to gene: EXOSC8. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | EXOSC8 | Arina Puzriakova reviewed gene: EXOSC8: Rating: AMBER; Mode of pathogenicity: None; Publications: 24989451; Phenotypes: Pontocerebellar hypoplasia type 1C, 616081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | DSCR3 | Arina Puzriakova commented on gene: DSCR3: Added new-gene-name tag, new approved HGNC gene symbol is VPS26C. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | DSCR3 | Arina Puzriakova Tag new-gene-name tag was added to gene: DSCR3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | DSCR3 | Arina Puzriakova Classified gene: DSCR3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | DSCR3 | Arina Puzriakova Added comment: Comment on list classification: Currently not associated with any phenotype in OMIM or G2P. Variants only found in one family - additional cases required to validate pathogenicity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.204 | DSCR3 | Arina Puzriakova Gene: dscr3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.203 | ATP6AP1 | Arina Puzriakova Classified gene: ATP6AP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.203 | ATP6AP1 | Arina Puzriakova Added comment: Comment on list classification: Unclear whether other ATP6AP1 variants are associated with a neurological phenotype. Amber rating in view of the mild ID phenotype, as a more significant, or consistent pattern, of DD/ID is required (added to watchlist). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.203 | ATP6AP1 | Arina Puzriakova Gene: atp6ap1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.202 | ATP6AP1 | Arina Puzriakova Tag watchlist tag was added to gene: ATP6AP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.202 | ATP6AP1 | Arina Puzriakova reviewed gene: ATP6AP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27231034; Phenotypes: Immunodeficiency, 300972, Hepatopathy, Intellectual disability, Cutis laxa, Epilepsy; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.202 | PDE10A | Arina Puzriakova Classified gene: PDE10A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.202 | PDE10A | Arina Puzriakova Added comment: Comment on list classification: Only mild cognitive delay reported in one family. Additional cases with a more significant, or consistent pattern, of DD/ID required to ascertain the contribution of PDE10A variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.202 | PDE10A | Arina Puzriakova Gene: pde10a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | PDE10A | Arina Puzriakova reviewed gene: PDE10A: Rating: AMBER; Mode of pathogenicity: None; Publications: 27058446; Phenotypes: Dyskinesia, limb and orofacial, infantile-onset, 616921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | LARS |
Konstantinos Varvagiannis gene: LARS was added gene: LARS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LARS were set to 32699352 Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438 Penetrance for gene: LARS were set to Complete Review for gene: LARS was set to GREEN Added comment: Please consider inclusion with amber/green rating in the current panel. Biallelic pathogenic LARS1 variants cause Infantile liver failure syndrome 1, MIM# 615438. Lenz et al (2020 - PMID: 32699352) review the phenotype of 25 affected individuals from 15 families. Seizures occurred in 19/24 and were commonly associated with infections. Encephalopathic episodes (in 13 patients) accompanied by seizures up to status epilepticus occurred independently of hepatic decompensation. In addition 22/24 presented with neurodevelopmental delay. The authors comment that cognitive impairment was present in 13/17 individuals (mild-severe) whereas most presented with learning disabilities. These patients will be most likely investigated for their liver disease (although presentation was highly variable and/or very mild in few). The gene encodes a cytoplasmic amino-acyl tRNA synthetase (ARS) with neurologic manifestations observed in almost all patients (and seizures / DD and ID common to other disorders due to mutations in other genes encoding for ARSs). Please note that the HGNC approved symbol for this gene is LARS1. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | SMARCA2 | Konstantinos Varvagiannis reviewed gene: SMARCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32694869; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | MORC2 |
Konstantinos Varvagiannis gene: MORC2 was added gene: MORC2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MORC2 were set to https://doi.org/10.1016/j.ajhg.2020.06.013 Phenotypes for gene: MORC2 were set to Charcot-Marie-Tooth disease, axonal, type 2Z, MIM #616688 Penetrance for gene: MORC2 were set to unknown Mode of pathogenicity for gene: MORC2 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: MORC2 was set to GREEN Added comment: The current review is based on a recent report by Sacoto et al (2020 - https://doi.org/10.1016/j.ajhg.2020.06.013). While several previous studies focused on the phenotype of axonal motor and senory neuropathy in individuals with heterozygous MORC2 pathogenic variants (Charcot-Marie-Tooth disease, axonal, type 2Z, MIM #616688) some of them presented among others with hypotonia, muscle weakness, intellectual disability, microcephaly or hearing loss [refs provided by Sacoto et al - learning disabilities (in some patients) also listed in OMIM's clinical synopsis]. Sacoto et al present a cohort of 20 individuals having genetic testing for developmental delay or growth failure (with a single one for a diagnosis of sensorimotor neuropathy). Overlapping features included DD, ID (18/20 - mild to severe), short stature (18/20), microcephaly (15/20) and variable craniofacial dysmorphisms. The authors comment that features suggestive of neuropathy (weakness, hyporeflexia, abnormal EMG/NCS) were frequent but not the predominant complaint. EMG/NCS abnormalities were abnormal in 6 out of 10 subjects investigated in this cohort. Other findings included brain MRI abnormalities (12/18 - in 5/18 Leigh-like lesions), hearing loss (11/19) and pigmentary retinopathy in few (5). Affected subjects were found to harbor in all cases missense variants in the ATPase module of MORC2 [residues 1 to 494 - NM_001303256.1 - the module consists of an ATPase domain (aa 1-265), a transducer S5-like domain (266-494) and a coiled-coiled domain (CC1 - aa 282-361)]. Variants had occured mostly as de novo events although inheritance from a similarly affected parent was also reported. Some of them were recurring within this cohort and/or the literature eg. c.79G>A/p.Glu27Lys (x5), c.260C>T/p.Ser87Leu (x2), c.394C>T/p.Arg132Cys (4x), c.1164C>G/p.Ser388Arg (x2), c.1181A>G/p.Tyr394Cys (x3). MORC2 encodes an ATPase involved in chromatin remodeling, DNA repair and transcriptional regulation. Chromatin remodeling and epigenetic silencing by MORC2 is mediated by the HUSH (Human Silencing Hub) complex. Functional studies (MORC2-knockout HeLa cells harboring a HUSH-sensitive GFP reporter were transduced with wt or mt MORC2 followed by measurement of reporter repression) supported the deleterious effect of most variants known at the time (hyperactivation of HUSH-mediating silencing, in line with previous observations). Overall this gene can be considered for inclusion in the ID panel with green rating. Also other gene panels (e.g. for short stature, microcephaly, hearing loss, pigmentary retinopathy, etc) if it meets the respective criteria for inclusion. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | HIST1H4J |
Arina Puzriakova changed review comment from: This is a possible gene for intellectual disability with facial dysmorphism in G2P. Tessadori et al. (2020) (PMID: 31804630) reported a 14-year old Hispanic male with profound intellectual disability, who was heterozygous for a de novo (c.274 A>G, p.K91E) variant in HIST1H4J. Clinical features were said to resemble those reported in patients with HIST1H4C variants, which encodes an identical H4 protein to that of HIST1H4J. Functional data obtained in zebrafish showed the missense variant caused developmental defects, specifically resulting in defective head structures and reduced body axis length.; to: Added new-gene-name tag, new approved HGNC gene symbol is H4C11. This is a possible gene for intellectual disability with facial dysmorphism in G2P. Tessadori et al. (2020) (PMID: 31804630) reported a 14-year old Hispanic male with profound intellectual disability, who was heterozygous for a de novo (c.274 A>G, p.K91E) variant in HIST1H4J. Clinical features were said to resemble those reported in patients with HIST1H4C variants, which encodes an identical H4 protein to that of HIST1H4J. Functional data obtained in zebrafish showed the missense variant caused developmental defects, specifically resulting in defective head structures and reduced body axis length. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | HIST1H4J | Arina Puzriakova Classified gene: HIST1H4J as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | HIST1H4J | Arina Puzriakova Added comment: Comment on list classification: Amber rating as additional cases are required to validate pathogenicity, but added to watchlist. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.201 | HIST1H4J | Arina Puzriakova Gene: hist1h4j has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.200 | HIST1H4J | Arina Puzriakova reviewed gene: HIST1H4J: Rating: AMBER; Mode of pathogenicity: None; Publications: 31804630; Phenotypes: Microcephaly, Intellectual disability, Dysmorphic facial features, Growth delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.200 | ADAMTS10 | Arina Puzriakova edited their review of gene: ADAMTS10: Changed publications: 15368195, 18567016, 19836009, 25469541 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.200 | ADAMTS10 | Arina Puzriakova Classified gene: ADAMTS10 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.200 | ADAMTS10 | Arina Puzriakova Added comment: Comment on list classification: While mild ID is reportedly a phenotypic feature associated with Weill–Marchesani syndrome, this is not evident in the literature cases. Therefore, a more consistent and/or significant pattern of ID is necessary for inclusion of ADAMTS10 on a diagnostic ID panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.200 | ADAMTS10 | Arina Puzriakova Gene: adamts10 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.199 | ADAMTS10 | Arina Puzriakova reviewed gene: ADAMTS10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15368195, 18567016, 19836009; Phenotypes: Weill-Marchesani syndrome, 277600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.199 | TOMM70 | Eleanor Williams Classified gene: TOMM70 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.199 | TOMM70 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team it was decided to rate this gene as Amber for now, until a clearer phenotype is established and the predominant mode of inheritance is determined. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.199 | TOMM70 | Eleanor Williams Gene: tomm70 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.198 | LZTFL1 | Arina Puzriakova Classified gene: LZTFL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.198 | LZTFL1 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.198 | LZTFL1 | Arina Puzriakova Gene: lztfl1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.197 | LZTFL1 |
Arina Puzriakova changed review comment from: Associated with phenotype in OMIM and probable in G2P. Biallelic variants in the LZTFL1 gene are an established cause of BBS17, with supporting functional data. Cognitive impairment is a feature of the BBS17 associated phenotype in all cases reported to date. Two families have been reported in literature - PMID: 22510444 (2012) - cognitive impairment reported in a 10-year-old BBS17 patient, harbouring a homozygous 5 bp deletion leading to a premature stop codon (c.402-406del, p.Pro136ThrfsX5) in LZTFL1.; to: Associated with phenotype in OMIM and probable in G2P. Biallelic variants in the LZTFL1 gene are an established cause of BBS17, with supporting functional data. Cognitive impairment is a feature of the BBS17 associated phenotype in all cases reported in literature to date: PMID: 22510444 (2012) - cognitive impairment reported in a 10-year-old BBS17 patient, harbouring a homozygous 5 bp deletion leading to a premature stop codon (c.402-406del, p.Pro136ThrfsX5) in LZTFL1. PMID: 23692385 (2014) - cognitive impairment reported in a pair of dizygotic twins with two compound heterozygous LZTFL1 variants ([c.260T>C, p.Leu87Pro];[c.778G>T, p.Glu260*]). One twin was said to have learning difficulties since childhood. She attended a specialised school, and at the age of 36, her educational level was equivalent to the elementary school level. The second twin was also reported to have scholastic difficulties and slowness with an educational level equivalent to primary school. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.197 | LYRM7 | Arina Puzriakova Classified gene: LYRM7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.197 | LYRM7 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.197 | LYRM7 | Arina Puzriakova Gene: lyrm7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.196 | LYRM7 | Arina Puzriakova Tag for-review tag was added to gene: LYRM7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.196 | LYRM7 |
Arina Puzriakova changed review comment from: PMID: 24014394 (2013) - Homozygous variant (c.73G>A) in LYRM7 identified in a patient with normal initial development until the first 20 months of life, when she presented rapid deterioration which included severe psychomotor regression. Functional studies performed in yeast indicate functional impairment. PMID: 26912632 (2016) - Six distinct homozygous variants in the LYRM7 gene were identified in seven affected individuals (including 2 sibs). Initial cognitive development was delayed in three patients and borderline in one.; to: PMID: 24014394 (2013) - Homozygous variant (c.73G>A) in LYRM7 identified in a patient with normal initial development until the first 20 months of life, when she presented rapid deterioration which included severe psychomotor regression. Functional studies performed in yeast indicate functional impairment. PMID: 26912632 (2016) - Six distinct homozygous variants in the LYRM7 gene were identified in seven affected individuals (including 2 sibs). Initial cognitive development was delayed in three patients and borderline in one. Continued development was delayed to variable degrees in five individuals, and all were said to have impaired intelligence at the time of the most recent assessment (aged 2.5-16 yrs). PMID: 28694194 (2017) - Three affected family members with homozygosity for a splice site deletion (c.243_244+2delGAGT) in LYRM7. Development was normal for the first few months of life, however all experienced a rapidly progressive clinical course which included profound impairment of psychomotor and mental functions. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.196 | LIPT1 | Arina Puzriakova Classified gene: LIPT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.196 | LIPT1 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - cognitive impairment has been reported in more than 3 unrelated surviving patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.196 | LIPT1 | Arina Puzriakova Gene: lipt1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.195 | LIPT1 | Arina Puzriakova Tag for-review tag was added to gene: LIPT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.195 | LIPT1 |
Arina Puzriakova changed review comment from: Associated with phenotype in OMIM and probable for Leigh syndrome with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase in G2P. LIPT1 deficiency, resulting from bi-allelic variants, is associated with developmental delay, epilepsy, and broad metabolic abnormalities. To date, five unrelated families have been reported with at least one affected child. PMID: 24341803 (2013) - In a boy with LIPT1 deficiency, exome sequencing revealed two heterozygous mutations (c.875C>G and c.535A>G). Psychomotor development was delayed from birth, but sudden further regression occurred at 18 months.; to: Associated with phenotype in OMIM and probable for Leigh syndrome with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase in G2P. LIPT1 deficiency, resulting from biallelic variants, is associated with developmental delay, epilepsy, and broad metabolic abnormalities. To date, five unrelated families have been reported with at least one affected child. PMID: 24341803 (2013) - In a boy with LIPT1 deficiency, exome sequencing revealed two compound heterozygous variants (c.875C>G and c.535A>G). Psychomotor development was delayed from birth, but sudden further regression occurred at 18 months. He could not speak but understood simple orders. He was otherwise fully conscious, alert, and he could smile, laugh and follow with eyes. Supporting functional data, including a yeast model. PMID: 29681092 (2018) – Compound heterozygous variants (c.212C>T and c.539T>C) identified in a male with seizures, severe lactic acidosis, and failure to thrive. Initially he was reportedly developmentally normal; however, due to subsequent neurodevelopmental regression, he had global developmental delays by 21-months-of-age. PMID 31042466 (2019) – In an 8-year-old female with developmental delay, seizures, and lactic acidosis, WES revealed two compound heterozygous variants (c.875C>G, c.131A>G). Two older sibs died of a similar condition at 7 months and 3 years. Sequencing was not possible in these individuals; however, a healthy sibling did not carry either variant. Functional analysis in patient-derived fibroblasts and mice confirmed LIPT1 deficiency. In two unrelated families, the phenotype resulted in early infant death, and therefore ID could not be assessed: PMID: 24256811 (2014) – compound heterozygous missense variants (c.212C>T and c.292C>G) were identified in a female that died on the ninth day of life. PMID: 27247813 (2016) – compound heterozygous nonsense variants (c.806G>A and c.980T>G) detected in two sibs who both died on the first day of life. A third sibling, who did not harbour these variants, was healthy and thriving at 12 months of life. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.195 | KLF7 | Arina Puzriakova Classified gene: KLF7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.195 | KLF7 | Arina Puzriakova Gene: klf7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.194 | KLF7 | Arina Puzriakova Classified gene: KLF7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.194 | KLF7 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - more than 3 unrelated cases presenting the relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.194 | KLF7 | Arina Puzriakova Gene: klf7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.193 | KLF7 | Arina Puzriakova Tag for-review tag was added to gene: KLF7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.193 | KLF7 |
Arina Puzriakova changed review comment from: Not associated with phenotype in OMIM or G2P. Powis et al. (2018) PMID: 29251763 - Heterozygous de novo missense variants were reported in four unrelated individuals. The two females (aged 15 and 16) were both said to have ID; while the two males (aged 2 and 4) had cognitive delay - though ID had not been formally assessed, presumably due to age. Additional features also included motor and speech delay, hypotonia, and neuromuscular symptoms.; to: Not associated with phenotype in OMIM or G2P. Powis et al. (2018) PMID: 29251763 - Heterozygous de novo missense variants were reported in four unrelated individuals. The two females (aged 15 and 16) were both said to have ID; while the two males (aged 2 and 4) had cognitive delay - though ID had not been formally assessed, presumably due to age. Additional features also included motor and speech delay, hypotonia, and neuromuscular symptoms. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.193 | KCNN3 | Arina Puzriakova Added comment: Comment on mode of pathogenicity: Gain-of-function variants identified in all patients, reported to date. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.193 | KCNN3 | Arina Puzriakova Mode of pathogenicity for gene: KCNN3 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.192 | KCNN3 | Arina Puzriakova Classified gene: KCNN3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.192 | KCNN3 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - three unrelated cases with relevant phenotype, although future re-evaluation of the two younger patients may be useful. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.192 | KCNN3 | Arina Puzriakova Gene: kcnn3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.191 | KCNN3 | Arina Puzriakova Tag for-review tag was added to gene: KCNN3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.191 | KCNN3 |
Arina Puzriakova changed review comment from: Associated with phenotype in OMIM, and probable gene-disease association in G2P. Bauer et al. (2019) PMID: 31155282 - De novo heterozygous gain-of-function variants identified in three unrelated individuals with ZimmermannLaband syndrome. Mild-moderate ID was reported in a 46-year-old man, while developmental delay was noted for the other two patients: a 4.5-year-old (first words at 2.5 y; attends nursery) and 5.5-year-old girl (limited spoken language; attends school with a personal aide). Additional features include coarse face, gingival hyperplasia, and/or nail hypo- or aplasia. ; to: Associated with phenotype in OMIM, and probable gene-disease association in G2P. Bauer et al. (2019) PMID: 31155282 - De novo heterozygous gain-of-function variants identified in three unrelated individuals with ZimmermannLaband syndrome. Mild-moderate ID was reported in a 46-year-old man, while developmental delay was noted for the other two patients: a 4.5-year-old (first words at 2.5 y; attends nursery) and 5.5-year-old girl (limited spoken language; attends school with a personal aide). Additional features include coarse face, gingival hyperplasia, and/or nail hypo- or aplasia. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.191 | GPC4 | Arina Puzriakova Mode of inheritance for gene: GPC4 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, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.190 | GPC4 | Arina Puzriakova Classified gene: GPC4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.190 | GPC4 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - more than 3 unrelated cases presenting the relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.190 | GPC4 | Arina Puzriakova Gene: gpc4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.189 | GPC4 |
Arina Puzriakova Tag for-review tag was added to gene: GPC4. Tag Skewed X-inactivation tag was added to gene: GPC4. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.189 | GPC4 |
Arina Puzriakova changed review comment from: Associated with phenotype in OMIM and a confirmed gene in G2P. Amor et al. (2019) (PMID: 30982611) reported ten affected males from six familes, each harbouring distinct GPC4 variants. All identified variants were truncating or resulted in a frameshift, suggesting loss of function as the likely disease mechanism. Variable degrees of ID (mild-moderate) were reported in 8/10 participants. Some supporting functional data. ; to: Associated with phenotype in OMIM and a confirmed gene for Keipert syndrome in G2P. Amor et al. (2019) (PMID: 30982611) reported ten affected males from six familes, each harbouring distinct GPC4 variants. All identified variants were truncating or resulted in a frameshift, suggesting loss of function as the likely disease mechanism. Variable degrees of ID (mild-moderate) were reported in 8/10 participants. Some supporting functional data. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.189 | IQSEC3 | Arina Puzriakova Classified gene: IQSEC3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.189 | IQSEC3 | Arina Puzriakova Gene: iqsec3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.188 | EIF2AK1 | Arina Puzriakova Classified gene: EIF2AK1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.188 | EIF2AK1 | Arina Puzriakova Added comment: Comment on list classification: Phenotype not relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.188 | EIF2AK1 | Arina Puzriakova Gene: eif2ak1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.187 | EIF2A | Arina Puzriakova Classified gene: EIF2A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.187 | EIF2A | Arina Puzriakova Gene: eif2a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.186 | DNM1L | Arina Puzriakova Classified gene: DNM1L as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.186 | DNM1L | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - more than 3 unrelated cases with distinct variants, presenting with a relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.186 | DNM1L | Arina Puzriakova Gene: dnm1l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.185 | DNM1L | Arina Puzriakova Tag for-review tag was added to gene: DNM1L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.185 | DNM1L |
Arina Puzriakova changed review comment from: Associated with related phenotype in OMIM and 'probable' gene in G2P. Variants in DNM1L cause a chronic neurological disorder, which is commonly associated with neonatal lethality. Global developmental delay or cognitive impairment (mild-profound) is reported in several surviving patients: PMID: 26931468 - Two unrelated cases: A male with global developmental delay, hypotonia and status epilepticus. WES revealed a c.1048G>A, p.G350R variant, for which low-level (68%) mosaicism was detected in the maternal sample.; to: Associated with related phenotype in OMIM and 'probable' gene in G2P. Variants in DNM1L cause a chronic neurological disorder, which is commonly associated with neonatal lethality. Global developmental delay or cognitive impairment (mild-profound) is reported in several surviving patients: PMID: 26931468 - Two unrelated cases: A male with global developmental delay, hypotonia and status epilepticus. WES revealed a c.1048G>A, p.G350R variant, for which low-level (6–8%) mosaicism was detected in the maternal sample. The second patient, with diffuse hypotonia, global developmental delay, poor growth, and persistent elevation of lactate, was found to harbour a de novo DNM1L variant (c.1135G>A, p.E379K). However, another de novo change in the PDHA1 gene (c.448G>A, p.G150R) was also found, and the definitive contribution of each variant to the patients phenotype could not be ascertained. PMID: 27328748 - Compound heterozygous DNM1L variants (c.106A>G, p.Ser36Gly; c.346_347delGA, p.Glu116Lysfs*6) identified in two brothers (3 and 16-years-old) with psychomotor delay, ocular and cerebellar involvement, including mild cognitive impairment in the older brother. Some supporting functional evidence using patient fibroblasts and a yeast model. PMID: 27301544 - De novo missense variant (c.1217T>C, p.Leu406Ser) identified in a child who presented severe hypotonia, infantile spasms with suppression‐burst and a high level of lactate in CSF. Development was profoundly delayed, and he attained no developmental milestones before his death at 18 months of age. PMID: 26604000 - De novo missense substitution, (c.1085G>A; p.Gly362Asp) identified in a child with refractory epilepsy. Profound global developmental delay was reported, and at the last clinical assessment (age 7 years), he remained nonambulatory with the use of <10 monosyllabic words. PMID: 26992161 - De novo heterozygous c.1084G>A (p.Gly362Ser) variant. Developmental delay was reported from 6-months of age, and at 2-years-old he was said to not be able to utter any intelligible words. There are also reports of an identical de novo heterozygous missense variant (p.R403C) in four unrelated individuals who all experienced normal development until a sudden-onset episode of status epilepticus at the age of 4, 5, 10, and 11-years-old, respectively. Subsequently, all presented with rapid neurological regression, diffuse cerebral atrophy and substantial cognitive decline. Functional studies showed the variant confers a dominant negative effect (PMID: 27145208; 30767894; 30711678). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.185 | ATAD1 |
Arina Puzriakova Tag treatable tag was added to gene: ATAD1. Tag for-review tag was added to gene: ATAD1. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.185 | ATAD1 | Arina Puzriakova Classified gene: ATAD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.185 | ATAD1 | Arina Puzriakova Added comment: Comment on list classification: Multiple affected individuals from 3 unrelated families. There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.185 | ATAD1 | Arina Puzriakova Gene: atad1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.184 | ATAD1 |
Arina Puzriakova changed review comment from: Not associated with any phenotype in G2P. Pathogenic variants have been described in seven affected individuals (three distinct consanguineous families) including a homozygous nonsense (c.826G>T; p.Glu276*), frameshift (c.1070_1071delAT; p.His357Argfs*15), and missense (c.162G>C; p.Gln54His) variant in the ATAD1 gene. Patients present with severe neurological features of essentially total absence of psychomotor development, encephalopathy, extreme hypertonia, non-responsiveness to stimuli, and death within the first few months of life. ; to: Not associated with any phenotype in G2P. Pathogenic variants have been described in seven affected individuals (three distinct consanguineous families) including a homozygous nonsense (c.826G>T; p.Glu276*), frameshift (c.1070_1071delAT; p.His357Argfs*15), and missense (c.162G>C; p.Gln54His) variant in the ATAD1 gene. Patients present with severe neurological features of essentially total absence of psychomotor development, encephalopathy, extreme hypertonia, non-responsiveness to stimuli, and death within the first few months of life. Knockout mouse model recapitulates phenotype. ATAD1 encodes Thorase, a mediator of AMPA receptor recycling; and therefore it was postulated that pathogenesis is a result of excessive AMPA receptor activity. Targeted therapy using perampanel, an AMPA receptor antagonist, ameliorated disease in both mice and humans, thus further supporting the role of ATAD1. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.184 | ADD3 | Arina Puzriakova Classified gene: ADD3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.184 | ADD3 | Arina Puzriakova Added comment: Comment on list classification: More than 3 unrelated individuals with ID. There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.184 | ADD3 | Arina Puzriakova Gene: add3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | ADD3 | Arina Puzriakova Tag for-review tag was added to gene: ADD3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | ADD3 |
Arina Puzriakova changed review comment from: Biallelic missense variants identified in four families (ten affected patients). Not associated with any phenotype in G2P. OMIM entry currently based on PMID:23836506. PMID: 23836506 (2013) - Homozygous missense variant c.1100G>A (p.G367D). ADD3 first identified in a consanguineous Jordanian family affecting four members. ID severe in two individuals and moderate/borderline in the others, some functional work from fibroblasts. The paper focused on the main phenotype of inheritable cerebral palsy. ; to: Biallelic missense variants identified in four families (ten affected patients). Not associated with any phenotype in G2P. OMIM entry currently based on PMID: 23836506. PMID: 23836506 (2013) - Homozygous missense variant c.1100G>A (p.G367D). ADD3 first identified in a consanguineous Jordanian family affecting four members. ID severe in two individuals and moderate/borderline in the others, some functional work from fibroblasts. The paper focused on the main phenotype of inheritable cerebral palsy. PMID: 29768408 (2018) - Two families with ADD3 biallelic variants and one family with ADD3 and KAT2B missense variants. Individuals with ADD3 variants have similar phenotypes and individuals with KAT2B variants have an extension to phenotype with impaired kidney and heart function, also demonstrated with functional evidence in flies. ID was reported in 5/6 participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | LZTFL1 | Arina Puzriakova reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22510444, 23692385; Phenotypes: Bardet-Biedl syndrome 17, 615994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | LYRM7 | Arina Puzriakova reviewed gene: LYRM7: Rating: GREEN; Mode of pathogenicity: ; Publications: 24014394, 26912632, 28694194; Phenotypes: Mitochondrial complex III deficiency, nuclear type 8, 615838; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | LIPT1 | Arina Puzriakova reviewed gene: LIPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 24341803, 29681092, 31042466, 24256811, 27247813; Phenotypes: Lipoyltransferase 1 deficiency, 616299; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | KLF7 | Arina Puzriakova reviewed gene: KLF7: Rating: GREEN; Mode of pathogenicity: ; Publications: 29251763; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | KCNN3 | Arina Puzriakova reviewed gene: KCNN3: 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: 31155282; Phenotypes: Zimmermann-Laband syndrome 3, 618658; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | GPC4 | Arina Puzriakova reviewed gene: GPC4: Rating: GREEN; Mode of pathogenicity: ; Publications: 30982611; Phenotypes: Keipert syndrome, 301026; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | IQSEC3 | Arina Puzriakova reviewed gene: IQSEC3: Rating: RED; Mode of pathogenicity: ; Publications: 31130284; Phenotypes: Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | EIF2AK1 | Arina Puzriakova reviewed gene: EIF2AK1: Rating: RED; Mode of pathogenicity: ; Publications: 32197074; Phenotypes: Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome, 618878, ADHD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | EIF2A | Arina Puzriakova reviewed gene: EIF2A: Rating: RED; Mode of pathogenicity: ; Publications: 31130284; Phenotypes: Intellectual disability, Seizures, ASD; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | DNM1L | Arina Puzriakova reviewed gene: DNM1L: Rating: GREEN; Mode of pathogenicity: ; Publications: 27145208, 30767894, 30711678, 26931468, 27328748, 27301544, 26604000, 26992161; Phenotypes: Epileptic encephalopathy, 614388, Global developmental delay, Cerebral atrophy, Microcephaly; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | ATAD1 | Arina Puzriakova reviewed gene: ATAD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28180185, 29390050, 29659736; Phenotypes: Encephalopathy, Progressive hypertonia, Seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.183 | ADD3 | Arina Puzriakova reviewed gene: ADD3: Rating: GREEN; Mode of pathogenicity: ; Publications: 23836506, 29768408; Phenotypes: Cerebral palsy, spastic quadriplegic, 617008, Intellectual disability, Microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.182 | ASTN1 | Arina Puzriakova Tag watchlist tag was added to gene: ASTN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.182 | ASTN1 | Arina Puzriakova Classified gene: ASTN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.182 | ASTN1 | Arina Puzriakova Added comment: Comment on list classification: As limited segregation and case-specific details for the individual identified in the second study (PMID:27431290), rating Amber until further cases reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.182 | ASTN1 | Arina Puzriakova Gene: astn1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.181 | ASTN1 | Arina Puzriakova reviewed gene: ASTN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26539891, 27431290, 29706646; Phenotypes: Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.181 | GNAI2 | Arina Puzriakova Classified gene: GNAI2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.181 | GNAI2 | Arina Puzriakova Gene: gnai2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.180 | FEM1B | Arina Puzriakova Mode of inheritance for gene: FEM1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova edited their review of gene: FEM1B: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.179 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Classified gene: FEM1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Added comment: Comment on list classification: Although phenotypic overlap is noted, it is not possible to ascertain whether the additional cases refer to different individuals. Also possible founder effect as all cases harbour the same variant. Additional cases/functional data are required to ascertain the contribution of FEM1B variants to an ID phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.178 | FEM1B | Arina Puzriakova Gene: fem1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.177 | FEM1B |
Arina Puzriakova changed review comment from: Gene not associated with any phenotype on OMIM or G2P. Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery study and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher. It is said that the three patients share a similar phenotype; however, any further details are limited and it is not possible to ascertain whether the additional cases refer to different individuals. No function analysis was undertaken to validate the implication of FEM1B.; to: Gene not associated with any phenotype on OMIM or G2P. Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery study and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher, who were said to share a similar phenotype. No function analysis was undertaken to validate the implication of FEM1B. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.177 | CCDC32 | Eleanor Williams Tag watchlist tag was added to gene: CCDC32. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.177 | CCDC32 | Eleanor Williams Classified gene: CCDC32 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.177 | CCDC32 | Eleanor Williams Added comment: Comment on list classification: Rating amber as 2 cases plus some limited functional evidence. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.177 | CCDC32 | Eleanor Williams Gene: ccdc32 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.176 | CCDC32 |
Eleanor Williams gene: CCDC32 was added gene: CCDC32 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC32 were set to 32307552 Phenotypes for gene: CCDC32 were set to global developmental delay Review for gene: CCDC32 was set to AMBER Added comment: PMID: 32307552 - Harel et al 2020 - report 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. In one family the child had global developmental delay, in the other the child had moderately delayed motor and language development and hyperactivity. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and demonstrate a contribution of ccdc32 in craniofacial, brain and left/right axis development. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Zornitza Stark edited their review of gene: ATL1: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Zornitza Stark edited their review of gene: ATL1: Changed publications: 21336785, 28736820, 29180453, 29691679, 31236401; Changed phenotypes: Neuropathy, hereditary sensory, type ID, MIM# 613708, Spastic paraplegia 3A, autosomal dominant, MIM# 182600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Zornitza Stark changed review comment from: Please note additional recent publications. Principal association is with HSP phenotype, often of later onset. Few reports of intellectual disability as part of this condition.; to: Please note additional recent publications. Principal association is with HSP/neuropathy phenotype, often of later onset. Few reports of intellectual disability as part of this condition (two families). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Zornitza Stark changed review comment from: Please note additional recent publications; to: Please note additional recent publications. Principal association is with HSP phenotype, often of later onset. Few reports of intellectual disability as part of this condition. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Zornitza Stark edited their review of gene: ATL1: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Sarah Leigh commented on gene: ATL1: The "for-review" tag has been added to this gene as there is enough evidence for this gene to be rated RED at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Sarah Leigh changed review comment from: Associated with phenotype in OMIM, not in G2P. Mild late onset mental retardation in 10 members of a three generation family with Spastic paraplegia 3A, autosomal dominant 182600; to: Associated with phenotype in OMIM, not in G2P. Mild to severe late onset mental retardation in 10 members of a three generation family with Spastic paraplegia 3A, autosomal dominant 182600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Sarah Leigh Tag for-review tag was added to gene: ATL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Sarah Leigh commented on gene: ATL1: Associated with phenotype in OMIM, not in G2P. Mental retardation has been reported in a second family (PMID 31236401). In this publication, the 9 year old proband and his maternal grandfather had hereditary spastic paraplegia and intellectual disability, however, proband's mother had hereditary spastic paraplegia, but no intelectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.175 | ATL1 | Sarah Leigh Publications for gene: ATL1 were set to 21336785; 28736820; 29180453; 29691679 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.174 | FEM1B |
Arina Puzriakova changed review comment from: Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery studying and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher. It is said that the three patients share a similar phenotype; however, any further details are limited and it is not possible to ascertain whether the additional patients refer to different individuals. No function analysis was undertaken to validate the implication of FEM1B. Gene not associated with any phenotype on OMIM or G2P.; to: Gene not associated with any phenotype on OMIM or G2P. Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery study and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher. It is said that the three patients share a similar phenotype; however, any further details are limited and it is not possible to ascertain whether the additional cases refer to different individuals. No function analysis was undertaken to validate the implication of FEM1B. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.174 | PTPN23 | Eleanor Williams Added comment: Comment on phenotypes: Added disease association from OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.174 | PTPN23 | Eleanor Williams Phenotypes for gene: PTPN23 were changed from Developmental epileptic encephalopathy with hypomyelination and brain atrophy; Intellectual disability; Severe developmental delay, to Developmental epileptic encephalopathy with hypomyelination and brain; Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity MIM#618890 atrophy; Intellectual disability; Severe developmental delay, | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.173 | GRIA2 | Eleanor Williams Added comment: Comment on phenotypes: Added disease association which has been added to OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.173 | GRIA2 | Eleanor Williams Phenotypes for gene: GRIA2 were changed from Epileptic encephalopathy intellectual disability stereotypic hand movements to Epileptic encephalopathy intellectual disability stereotypic hand movements; Neurodevelopmental disorder with language impairment and behavioral abnormalities MIM#618917 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.172 | FBXW11 | Eleanor Williams Added comment: Comment on phenotypes: Added disease association which has been added in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.172 | FBXW11 | Eleanor Williams Phenotypes for gene: FBXW11 were changed from Global developmental delay; Intellectual disability; Abnormality of the eye; Abnormality of the head; Abnormality of digit to Global developmental delay; Intellectual disability; Abnormality of the eye; Abnormality of the head; Abnormality of digit; Neurodevelopmental, jaw, eye, and digital syndrome MIM#618914 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.171 | CARS | Eleanor Williams Added comment: Comment on phenotypes: Added disease term which has now been added to OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.171 | CARS | Eleanor Williams Phenotypes for gene: CARS were changed from Brittle hair; Fragile nails; Microcephaly; Neurodevelopmental delay to Brittle hair; Fragile nails; Microcephaly; Neurodevelopmental delay; Microcephaly, developmental delay, and brittle hair syndrome MIM#618891 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | ADARB1 |
Arina Puzriakova changed review comment from: Variants reported in four unrelated individuals with severe/profound intellectual disability, microcephaly, and seizures. Functional studies demonstrate variants result in reduction of ADARB1 product activity or changes in splicing (PMID: 32220291). Homozygous knockout mice presented with seizures and early death, supporting the role of ADARB1 in brain function (PMID: 10894545) Gene is associated with phenotype in OMIM and G2P.; to: Gene is associated with phenotype in OMIM and G2P. PMID: 32220291 - Bi-allelic variants reported in four unrelated individuals with severe/profound intellectual disability, microcephaly, and seizures. Functional studies demonstrate variants result in reduction in ADARB1 product activity or changes in splicing. PMID: 10894545 - Homozygous knockout mice presented with siezures and early death, supporting the role of ADARB1 in brain function. This gene has also been added to the Genetic Epilepsy and Severe Microcephaly panels with a suggested Green classification at the next major review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | CNPY3 |
Konstantinos Varvagiannis gene: CNPY3 was added gene: CNPY3 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CNPY3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CNPY3 were set to 29394991; 30237576 Phenotypes for gene: CNPY3 were set to Epileptic encephalopathy, early infantile, 60 (MIM 617929) Penetrance for gene: CNPY3 were set to Complete Review for gene: CNPY3 was set to GREEN Added comment: Biallelic CNPY3 mutations cause Epileptic encephalopathy, early infantile, 60 (MIM 617929). The phenotype including among others hypotonia, intractable seizures, DD and ID has been first reported by Mutoh et al (2018 - PMID: 29394991) in 3 subjects from 2 families. Evidence was provided for the role of the gene (incl. mouse model) and pathogenicity of the identified variants (resulting in LoF). Another subject with similar features of hypotonia, DD, intractable epilepsy, feeding problems has been described briefly by Maddirevula et al (2019 - PMID: 30237576). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | KIF21B |
Konstantinos Varvagiannis gene: KIF21B was added gene: KIF21B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KIF21B were set to 32415109 Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly Penetrance for gene: KIF21B were set to unknown Mode of pathogenicity for gene: KIF21B 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: KIF21B was set to GREEN Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | PAX1 |
Konstantinos Varvagiannis gene: PAX1 was added gene: PAX1 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: PAX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAX1 were set to 29681087; 23851939; 28657137 Phenotypes for gene: PAX1 were set to Otofaciocervical syndrome 2, 615560 Penetrance for gene: PAX1 were set to Complete Review for gene: PAX1 was set to AMBER Added comment: Biallelic PAX1 pathogenic variants cause Otofaciocervical syndrome 2 (OMIM 615560). Brief review of the literature suggests 3 relevant publications to date (04-07-2020). 2 individuals with DD and ID have been reported (Patil et al, 2018 - PMID: 29681087 and Pohl et al, 2013 - PMID: 23851939). Other subjects reported were only evaluated as newborns(mostly)/infants [Paganini et al, 2017 - PMID: 28657137, Patil et al, 2018 - PMID: 29681087]. While the first report by Pohl et al identified a homozygous missense variant supported by functional studies [NM_006192.5:c.497G>T - p.(Gly166Val)] subsequent ones identified homozygosity for pLoF mutations [Patil et al: NM_006192.4:c.1173_1174insGCCCG / Paganini et al: NM_006192:c.1104C>A - p.(Cys368*)]. As discussed by Pohl et al: PAX1 encodes a transcription factor with critical role in pattern formation during embryogenesis. Study of the mouse Gly157Val (equivalent to human Gly166Val) Pax1 variant suggested reduced binding affinity (reduced transactivation of a regulatory sequence of the Nkx3-2 promoter) and hypofunctional nature of this variant. Mouse models seem to recapitulate features of the disorder (skeletal, immunodeficiency) while the role of Pax1 in hearing process was thought to be supported by early expression (P6) in mouse cochlea. Overall this gene can be considered for inclusion in the ID panel with amber/green rating. Sources: Literature, Radboud University Medical Center, Nijmegen |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | TMEM106B |
Konstantinos Varvagiannis gene: TMEM106B was added gene: TMEM106B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021 Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964) Penetrance for gene: TMEM106B were set to Complete Mode of pathogenicity for gene: TMEM106B 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: TMEM106B was set to GREEN Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021). While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al]. All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al). As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin. Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect. Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel. Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | TBC1D2B |
Konstantinos Varvagiannis gene: TBC1D2B was added gene: TBC1D2B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D2B were set to 32623794 Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality Penetrance for gene: TBC1D2B were set to Complete Review for gene: TBC1D2B was set to AMBER Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24. Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | EXOC2 |
Konstantinos Varvagiannis gene: EXOC2 was added gene: EXOC2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC2 were set to 32639540 Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology Penetrance for gene: EXOC2 were set to Complete Review for gene: EXOC2 was set to AMBER Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | CEP120 |
Konstantinos Varvagiannis gene: CEP120 was added gene: CEP120 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP120 were set to 27208211 Phenotypes for gene: CEP120 were set to Joubert syndrome 31 (MIM 617761); Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300) Penetrance for gene: CEP120 were set to Complete Review for gene: CEP120 was set to GREEN Added comment: Pathogenic CEP120 variants have been reported in recessive ciliopathies, namely Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300) and Joubert syndrome 31 (MIM 617761). The former is associated with a severe/lethal outcome (4 unrelated infants described by Shaheen et al 2015 - PMID: 25361962, 2 fetuses reported by Roosing et al 2016 - PMID: 27208211). Roosing et al however, also provided details on 4 unrelated subjects with Joubert syndrome diagnosis. All presented with a neurologic phenotype of hypotonia, DD, cognitive impairment and exhibited a molar tooth sign. As a result, this gene can be considered for inclusion in the ID panel with green rating (>3 individuals/variants, consistent ciliopathy phenotype). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | CCDC174 |
Konstantinos Varvagiannis gene: CCDC174 was added gene: CCDC174 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC174 were set to 26358778 Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816 Penetrance for gene: CCDC174 were set to Complete Mode of pathogenicity for gene: CCDC174 was set to Other Review for gene: CCDC174 was set to AMBER Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | ACOX2 |
Konstantinos Varvagiannis gene: ACOX2 was added gene: ACOX2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACOX2 were set to 27647924; 27884763; 29287774 Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6 - 617308 Penetrance for gene: ACOX2 were set to unknown Review for gene: ACOX2 was set to RED Added comment: Biallelic pathogenic ACOX2 variants cause Bile acid synthesis defect, congenital, 6 (MIM 617308). Overall the phenotype corresponds to an IEM/peroxisomal disorder. As per 01-07-2020 there are 3 reports, briefly reviewed : - Vilarinho et al [2016 - PMID: 27647924] provided details on an 8-year-old boy with ID. - Monte et al [2017 - PMID: 27884763] described a 16 year old male with sustained elevation of transaminases *without* accompanying neurologic symptomatology (as they comment). - Ferdinandusse et al [2018 - PMID: 29287774] reported on a girl deceased at the age of few months. Please consider inclusion in the ID panel with amber/red rating pending further reports. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | ABCA2 |
Konstantinos Varvagiannis gene: ABCA2 was added gene: ABCA2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799 Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 Penetrance for gene: ABCA2 were set to Complete Review for gene: ABCA2 was set to GREEN Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | HERC2 |
Konstantinos Varvagiannis edited their review of gene: HERC2: Added comment: Please consider upgrading this gene to green in the current panel based on the following updated review (13-07-2020): Biallelic pathogenic HERC2 variants cause Mental retardation, autosomal recessive 38 (MIM 615516). The current review is based mostly on the information provided by Elpidorou et al (2020 - PMID: 32571899) summarizing the findings in several affected individuals as published in the literature. ID was a universal feature among them (27/27) and seizures were reported in some (9/27): - 22 subjects from Amish/Mennonite families were homozygous for p.Pro594Leu [NM_004667.5(HERC2):c.1781C>T] (Puffenberger et al 2012 - PMID: 23065719, Harlalka et al 2013 - PMID: 23243086, Abraham et al - PMID: 30902390) - 2 additional patients were homozygous for another missense SNV [NM_004667.5(HERC2):c.4625G>A - p.Arg1542His] (Abraham et al 2019 - PMID: 30902390) - 3 sibs born to consanguineous parents, homozygous for NM_004667.5:c.13767_13770delTGAA - p.(Asn4589LysTer4598)] as described by Elpidorou et al. - 1 male homozygous 286 kb deletion spanning several 5' exons of HERC2 as well as the first exons of OCA2 was described by Morice-Picard et al (2016 - PMID: 27759030). Despite a neurological presentation (axial hypotonia, peripheral hypertonia, extrapyramidal symptoms and uncoordinated movements) further information was not available. Apart from the cases summarized by Elpidorou et al, there have been few additional ones e.g. : - Trujillano et al (2017 - PMID: 27848944) reported briefly on a patient, homozygous for NM_004667.5:c.4676-1G>A displaying seizures, hypotonia, global DD, "Encephalopathy" and abnormality of the liver. - Yavarna et al (2015 - PMID: 26077850) provided few details with on an individual with primarily 'neurocognitive' phenotype but rather atypical presentation (MRI abnormalities, TGA, VSD, renal anomaly, growth retardation, hearing loss) due to p.Q3164X variant (recessive inheritance was specified). Several lines of evidence support an important role for the protein encoded (an E3 ubiquitin protein ligase, interacting also with UBE3A, involved in several cellular processes incl. cell cycle regulation, spindle formation during mitosis, mitochondrial functions, DNA damage responses by targeting proteins such as XPA) as well as the effect of the reported variants (mRNA studies, Western blot, detection of a fusion transcript in the case of the deletion, etc). Individuals from the Amish families displayed Angelman-like features (in line with HERC2-UBE3A interaction) with - among others - gait instability. Mouse models recapitulate some of these features (e.g. the movement disorder) as extensively discussed by Abraham et al. Overall this gene can be included in the ID and epilepsy panels with green rating. -----; Changed rating: GREEN; Changed publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | SEC31A | Sarah Leigh Classified gene: SEC31A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | SEC31A | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. One homozygous terminating variant reported in sibs of consanguineous Bedouin parents, together with a Drosophila model in which loss of sec31a was embryonically lethal and associated with defects in eye and brain development, consistent with abnormal neurodevelopment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.170 | SEC31A | Sarah Leigh Gene: sec31a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.169 | SEC31A | Sarah Leigh Phenotypes for gene: SEC31A were changed from Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, OMIM #618651 to Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies 618651 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.168 | SBF1 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 7 variants reported in at least 5 unrelated cases.; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 7 variants reported in at least 5 unrelated cases. The phenotypes vary, but early‐onset microcephaly and moderate‐severe developmental delay were reported in 3 cases (PMID 30039846, 21210780, 20658556). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.168 | SBF1 | Sarah Leigh Classified gene: SBF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.168 | SBF1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 7 variants reported in at least 5 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.168 | SBF1 | Sarah Leigh Gene: sbf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.167 | SBF1 | Sarah Leigh reviewed gene: SBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.167 | SBF1 | Sarah Leigh Tag for-review tag was added to gene: SBF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.167 | SBF1 | Sarah Leigh Phenotypes for gene: SBF1 were changed from Charcot-Marie-Tooth disease, type 4B3, MIM# 615284 to Charcot-Marie-Tooth disease, type 4B3 615284 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.166 | SARS2 | Sarah Leigh edited their review of gene: SARS2: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.166 | SARS2 | Sarah Leigh Tag for-review tag was added to gene: SARS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.166 | SARS2 | Sarah Leigh Classified gene: SARS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.166 | SARS2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in at least 3 unrelated cases. Segregates with the disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.166 | SARS2 | Sarah Leigh Gene: sars2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.165 | SARS2 | Sarah Leigh Publications for gene: SARS2 were set to 21255763; 24034276 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.164 | SARS2 | Sarah Leigh Phenotypes for gene: SARS2 were changed from Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845 to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.163 | RUSC2 | Sarah Leigh Classified gene: RUSC2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.163 | RUSC2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least 2 unrelated cases. No functional studies have been reported, although authors of PMID 27612186 suggest that p.R866* results in total loss of function as the sibs biallelic with this variant have a more severe phenotype than the case who is biallelic for p.R1318*, which they conclude results in partial loss of function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.163 | RUSC2 | Sarah Leigh Gene: rusc2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.162 | RUSC2 | Sarah Leigh Phenotypes for gene: RUSC2 were changed from Mental retardation, autosomal recessive 61, MIM# 617773 to Mental retardation, autosomal recessive 61 617773 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.161 | SLC12A6 | Sarah Leigh commented on gene: SLC12A6: For-review tag has been added as it maybe appropriate to change the MOI to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review, to ensure that de novo heterozgous variants are identified. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.161 | SLC12A6 | Sarah Leigh commented on gene: SLC12A6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.161 | SLC12A6 | Sarah Leigh Publications for gene: SLC12A6 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.160 | SLC12A6 | Sarah Leigh Tag for-review tag was added to gene: SLC12A6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.160 | RIC1 | Sarah Leigh Tag founder-effect tag was added to gene: RIC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.160 | GALNT2 | Sarah Leigh Classified gene: GALNT2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.160 | GALNT2 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.160 | GALNT2 | Sarah Leigh Gene: galnt2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.159 | GALNT2 |
Sarah Leigh gene: GALNT2 was added gene: GALNT2 was added to Intellectual disability. Sources: Literature for-review tags were added to gene: GALNT2. Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALNT2 were set to 27508872; 32293671 Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation, type IIt 618885 Review for gene: GALNT2 was set to GREEN Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 5 variants reported in at least 5 unrelated cases, together with mouse and rat models (PMID 27508872;32293671). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.158 | ADARB1 | Sarah Leigh Classified gene: ADARB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.158 | ADARB1 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.158 | ADARB1 | Sarah Leigh Gene: adarb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | ADARB1 | Sarah Leigh Tag for-review tag was added to gene: ADARB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | ALG14 | Sarah Leigh changed review comment from: Have added the "for review" tag, to address the phenotypic variability of published carriers of ALG14 variants.; to: Have added the "for review" tag, to address the phenotypic variability of published carriers of ALG14 variants. This will be reviewed as more cases are reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | ADARB1 | Arina Puzriakova reviewed gene: ADARB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32220291; Phenotypes: Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | SETD1A | Sarah Leigh reviewed gene: SETD1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | FEM1B | Arina Puzriakova edited their review of gene: FEM1B: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | FEM1B |
Arina Puzriakova changed review comment from: Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery studying and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher. It is said that the three patients share a similar phenotype; however, any further details are limited and it is not possible to ascertain whether the additional patients refer to different individuals. No function analysis was undertaken to validate the implication of FEM1B. Gene not associated with any phenotype on OMIM or G2P.; to: Lecoquierre et al. (2019) (PMID: 31036916) conducted a large candidate gene discovery studying and identified a de novo missense variant (p.Arg126Gln) in a patient with syndromic global developmental delay. Recurrence of the same variant was highlighted in an individual from the DDD study, and the another from GeneMatcher. It is said that the three patients share a similar phenotype; however, any further details are limited and it is not possible to ascertain whether the additional patients refer to different individuals. No function analysis was undertaken to validate the implication of FEM1B. Gene not associated with any phenotype on OMIM or G2P. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.157 | SETD1A | Sarah Leigh Publications for gene: SETD1A were set to 28135719; 26974950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.156 | GNAI2 | Arina Puzriakova reviewed gene: GNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31036916, 27787898; Phenotypes: Syndromic developmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.156 | NRROS | Sarah Leigh Phenotypes for gene: NRROS were changed from neurodegeneration; intracranial calcification; epilepsy to Seizures, early-onset, with neurodegeneration and brain calcification 618875 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.155 | NRROS | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.155 | NRROS | Sarah Leigh Classified gene: NRROS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.155 | NRROS | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for NRROS-related Infantile-Onset Neurodegeneration with Intracranial Calcification. At least 6 variants reported in at least 5 unrelated cases (PMIDs 32100099;32197075), together with supportive mouse model (PMID 28459434). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.155 | NRROS | Sarah Leigh Gene: nrros has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.154 | NRROS | Sarah Leigh Classified gene: NRROS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.154 | NRROS | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for NRROS-related Infantile-Onset Neurodegeneration with Intracranial Calcification. At least 6 variants reported in at least 5 unrelated cases (PMIDs 32100099;32197075), together with supportive mouse model (PMID 28459434). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.154 | NRROS | Sarah Leigh Gene: nrros has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.154 | NRROS | Sarah Leigh Publications for gene: NRROS were set to 32100099; 32197075 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NRROS | Sarah Leigh reviewed gene: NRROS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | FEM1B | Arina Puzriakova reviewed gene: FEM1B: Rating: RED; Mode of pathogenicity: None; Publications: 31036916; Phenotypes: Global developmental delay; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NOVA2 | Sarah Leigh Tag for-review tag was added to gene: NOVA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NOVA2 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NOVA2 | Sarah Leigh edited their review of gene: NOVA2: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NOVA2 | Sarah Leigh Classified gene: NOVA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NOVA2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 6 terminating variants reported in unrelated cases, together supportive functional studies in a zebrafish knockdown of the NOVA2 ortholog (nova1a) (PMID 32197073). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.153 | NOVA2 | Sarah Leigh Gene: nova2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.152 | NOVA2 | Sarah Leigh Classified gene: NOVA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.152 | NOVA2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 6 terminating variants reported in unrelated cases, together supportive functional studies in a zebrafish knockdown of the NOVA2 ortholog (nova1a) (PMID 32197073). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.152 | NOVA2 | Sarah Leigh Gene: nova2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.151 | NOVA2 | Sarah Leigh Phenotypes for gene: NOVA2 were changed from Intellectual disability; autism; hypotonia; spasticity; ataxia to Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities 618859 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.150 | CDK19 | Sarah Leigh Tag for-review tag was added to gene: CDK19. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.150 | CDK19 | Sarah Leigh Classified gene: CDK19 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.150 | CDK19 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive Drosophila, demonstating the effects of the variants (PMID 32330417). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.150 | CDK19 | Sarah Leigh Gene: cdk19 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.149 | CDK19 | Sarah Leigh Phenotypes for gene: CDK19 were changed from microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation to Epileptic encephalopathy, early infantile, 87 618916 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.148 | CDK19 | Sarah Leigh Publications for gene: CDK19 were set to 20563892 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.148 | CDK19 | Sarah Leigh Mode of inheritance for gene: CDK19 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.147 | WIPI2 | Sarah Leigh Classified gene: WIPI2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.147 | WIPI2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 homozygous variant was reported in 4 members of a consanguineous family. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.147 | WIPI2 | Sarah Leigh Gene: wipi2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.146 | WIPI2 | Sarah Leigh Phenotypes for gene: WIPI2 were changed from Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 to ?Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.145 | GSX2 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least 2 unrealated cases.; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least 2 unrealated cases, together with supportive functional studies (PMID 31412107). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.145 | GSX2 | Sarah Leigh Classified gene: GSX2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.145 | GSX2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least 2 unrealated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.145 | GSX2 | Sarah Leigh Gene: gsx2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.144 | YARS | Sarah Leigh changed review comment from: Comment on list classification: Biallelic variants in three families with complex clinical conditions including developmental delay.; to: Comment on list classification: Biallelic variants in three families with complex clinical conditions including developmental delay. PMID 30304524 reports an extended family with microcephaly, expressive language delay, hearing loss, amongst other features. PMID 29232904 reports a proband whose phenotype included hearing loss, retnititis pigmentosa and hypotonia, but did not include intellectual disability. PMID 27633801 reports two sibblings with hypotionia, the older brother at 15 years of age has mild delays, he attends school on an individualized educational program and functions at a grade 3 level. He speaks and understands English and Polish. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.144 | YARS | Sarah Leigh Classified gene: YARS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.144 | YARS | Sarah Leigh Added comment: Comment on list classification: Biallelic variants in three families with complex clinical conditions including developmental delay. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.144 | YARS | Sarah Leigh Gene: yars has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | YARS | Sarah Leigh Tag for-review was removed from gene: YARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | YARS | Sarah Leigh commented on gene: YARS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | YARS | Sarah Leigh Tag new-gene-name tag was added to gene: YARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | YARS | Sarah Leigh Tag for-review tag was added to gene: YARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | CACNB4 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | CACNB4 | Sarah Leigh Classified gene: CACNB4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | CACNB4 | Sarah Leigh Added comment: Comment on list classification: PMID 32176688 reports intellectual disability in homozygous sibs. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.143 | CACNB4 | Sarah Leigh Gene: cacnb4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.142 | CACNB4 | Sarah Leigh Classified gene: CACNB4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.142 | CACNB4 | Sarah Leigh Added comment: Comment on list classification: PMID 32176688 reports intellectual disability in homozygous sibs. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.142 | CACNB4 | Sarah Leigh Gene: cacnb4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.141 | CACNB4 | Sarah Leigh Mode of inheritance for gene: CACNB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.140 | CACNB4 | Sarah Leigh Publications for gene: CACNB4 were set to 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.139 | RSRC1 | Sarah Leigh commented on gene: RSRC1: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.139 | RSRC1 | Sarah Leigh Classified gene: RSRC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.139 | RSRC1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in unrelated families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.139 | RSRC1 | Sarah Leigh Gene: rsrc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.138 | RSRC1 | Sarah Leigh Tag for-review tag was added to gene: RSRC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.138 | RSRC1 | Sarah Leigh Publications for gene: RSRC1 were set to 28640246; 29522154; 32227164 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.137 | RSRC1 | Sarah Leigh Phenotypes for gene: RSRC1 were changed from Intellectual developmental disorder, autosomal recessive 70 618402 to Intellectual developmental disorder, autosomal recessive 70 618402 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.137 | RSRC1 | Sarah Leigh Publications for gene: RSRC1 were set to 28640246; 29522154; 32227164 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.136 | RSRC1 | Sarah Leigh Phenotypes for gene: RSRC1 were changed from Intellectual developmental disorder, autosomal recessive 70, MIM# 618402 to Intellectual developmental disorder, autosomal recessive 70 618402 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.136 | RSRC1 | Sarah Leigh Publications for gene: RSRC1 were set to 28640246; 29522154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.135 | SLC12A2 |
Zornitza Stark gene: SLC12A2 was added gene: SLC12A2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SLC12A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC12A2 were set to 30740830 Phenotypes for gene: SLC12A2 were set to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies Review for gene: SLC12A2 was set to GREEN gene: SLC12A2 was marked as current diagnostic Added comment: Two families reported and a mouse model. New report is not on PubMed yet: (https://doi.org/10.1212/NXG.0000000000000478) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.135 | RAP1GDS1 |
Zornitza Stark gene: RAP1GDS1 was added gene: RAP1GDS1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAP1GDS1 were set to 32431071 Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features Review for gene: RAP1GDS1 was set to AMBER Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected, borderline Red/Amber. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.135 | RIC1 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.135 | RIC1 | Sarah Leigh Publications for gene: RIC1 were set to 31932796 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.134 | RIC1 | Sarah Leigh Classified gene: RIC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.134 | RIC1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least one variant reported in numerous members of two families, who shared an autozygous interval, confirming Founder effect (PMID 27878435). Segregation was demonstrated, together with supportive functional and zebra fish model (PMID 31932796). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.134 | RIC1 | Sarah Leigh Gene: ric1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.134 | RIC1 | Sarah Leigh Classified gene: RIC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.134 | RIC1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least one variant reported in numerous members of two families, who shared an autozygous interval, confirming Founder effect (PMID 27878435). Segregation was demonstrated, together with supportive functional and zebra fish model (PMID 31932796). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.134 | RIC1 | Sarah Leigh Gene: ric1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.133 | RIC1 | Sarah Leigh Tag watchlist tag was added to gene: RIC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.133 | RIC1 | Sarah Leigh Phenotypes for gene: RIC1 were changed from Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD to CATIFA syndrome 618761; Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.132 | OTUD7A | Sarah Leigh Classified gene: OTUD7A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.132 | OTUD7A | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen, Although the region ISCA-46295-Loss, which encompasses the OTUD7A locus, is associated with seizures 20236110, mental retardation 22775350, dysmorphic features, developmental delay and severe epileptic encephalopathy. PMID 31997314 report a homozygous variant in a case of severe global developmental delay, language impairment and epileptic encephalopathy; segregation and functional studies support this gene disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.132 | OTUD7A | Sarah Leigh Gene: otud7a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.131 | ISCA-46295-Loss | Sarah Leigh Publications for Region: ISCA-46295-Loss were set to 19898479; 20236110; 22775350 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.130 | TOMM70 |
Eleanor Williams changed review comment from: Not associated with a disease phenotype in OMIM or Gene2Phenotype PMID: 31907385 - Wei et al 2020 - report a patient with severe anemia, lactic acidosis, and developmental delay in which two compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)] were identified. Functional studies showed that patient-derived cells exhibited multi-oxidative phosphorylation system (OXPHOS) complex defects. Abstract only accessed. PMID: 32356556 - Dutta et al 2020 - report 2 patients with de novo heterozygous missense variants in the C-terminal region of TOMM70. Both patients had shared symptoms including hypotonia, hyper-reflexia, ataxia, dystonia and significant white matter abnormalities. However, for patient 1 a neurodevelopmental disorder was noted in infancy, but patient 2 developed as normal until age 4 when neurological regression occurred. Some functional data from Drosophila show that the variants cause partial loss of function. 3 cases but different mode of inheritance and phenotypic presentation. Sources: Literature; to: Not associated with a disease phenotype in OMIM or Gene2Phenotype PMID: 31907385 - Wei et al 2020 - report a patient with severe anemia, lactic acidosis, and developmental delay in which two compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)] were identified. Functional studies showed that patient-derived cells exhibited multi-oxidative phosphorylation system (OXPHOS) complex defects. Abstract only accessed. PMID: 32356556 - Dutta et al 2020 - report 2 patients with de novo heterozygous missense variants in the C-terminal region of TOMM70. Both patients had shared symptoms including hypotonia, hyper-reflexia, ataxia, dystonia and significant white matter abnormalities. Patient 1 showed severe global developmental delay. However, for patient 1 a neurodevelopmental disorder was noted in infancy, but patient 2 developed as normal until age 4 when neurological regression occurred. Some functional data from Drosophila show that the variants cause partial loss of function. 3 cases but different mode of inheritance and phenotypic presentation. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.130 | TOMM70 |
Eleanor Williams gene: TOMM70 was added gene: TOMM70 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TOMM70 were set to 31907385; 32356556 Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis; developmental delay; white matter abnormalities Review for gene: TOMM70 was set to AMBER Added comment: Not associated with a disease phenotype in OMIM or Gene2Phenotype PMID: 31907385 - Wei et al 2020 - report a patient with severe anemia, lactic acidosis, and developmental delay in which two compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)] were identified. Functional studies showed that patient-derived cells exhibited multi-oxidative phosphorylation system (OXPHOS) complex defects. Abstract only accessed. PMID: 32356556 - Dutta et al 2020 - report 2 patients with de novo heterozygous missense variants in the C-terminal region of TOMM70. Both patients had shared symptoms including hypotonia, hyper-reflexia, ataxia, dystonia and significant white matter abnormalities. However, for patient 1 a neurodevelopmental disorder was noted in infancy, but patient 2 developed as normal until age 4 when neurological regression occurred. Some functional data from Drosophila show that the variants cause partial loss of function. 3 cases but different mode of inheritance and phenotypic presentation. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.129 | CAPZA2 | Eleanor Williams Phenotypes for gene: CAPZA2 were changed from to intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.128 | CAPZA2 | Eleanor Williams Classified gene: CAPZA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.128 | CAPZA2 | Eleanor Williams Added comment: Comment on list classification: 2 cases reported. Some functional evidence but not enough to promote to green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.128 | CAPZA2 | Eleanor Williams Gene: capza2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.127 | CAPZA2 |
Eleanor Williams gene: CAPZA2 was added gene: CAPZA2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CAPZA2 were set to 32338762 Review for gene: CAPZA2 was set to AMBER Added comment: Not associated with a disease phenotype in OMIM. PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.126 | HARS |
Zornitza Stark changed review comment from: 3 cases from 2 unrelated families with biallelic variants and mild to severe intellectual disability as a feature of the condition. Please note association with Usher syndrome (deafness/retinal phenotypes) has been assessed as 'refuted' by ClinGen, and this gene has a well-established association between heterozygous variants and CMT. Sources: Literature; to: 3 cases from 2 unrelated families with biallelic variants and mild to severe intellectual disability as a feature of the condition. We have also added to paediatric ataxia panel as Amber. Please note association with Usher syndrome (deafness/retinal phenotypes) has been assessed as 'refuted' by ClinGen, and this gene has a well-established association between heterozygous variants and CMT. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.126 | HARS |
Zornitza Stark gene: HARS was added gene: HARS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HARS were set to 32296180 Phenotypes for gene: HARS were set to multisystem ataxic syndrome; mild-severe intellectual disability Review for gene: HARS was set to AMBER Added comment: 3 cases from 2 unrelated families with biallelic variants and mild to severe intellectual disability as a feature of the condition. Please note association with Usher syndrome (deafness/retinal phenotypes) has been assessed as 'refuted' by ClinGen, and this gene has a well-established association between heterozygous variants and CMT. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.126 | EXOC7 |
Zornitza Stark gene: EXOC7 was added gene: EXOC7 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC7 were set to 32103185 Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly Review for gene: EXOC7 was set to GREEN gene: EXOC7 was marked as current diagnostic Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration. We have added to the Microcephaly and Genetic Epilepsies panels as well. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.126 | HNRNPH1 |
Zornitza Stark gene: HNRNPH1 was added gene: HNRNPH1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPH1 were set to 32335897; 29938792 Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability Review for gene: HNRNPH1 was set to GREEN Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.126 | PDCD6IP |
Zornitza Stark gene: PDCD6IP was added gene: PDCD6IP was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDCD6IP were set to 32286682 Phenotypes for gene: PDCD6IP were set to microcephaly; Intellectual disability Review for gene: PDCD6IP was set to AMBER Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.126 | MCM3AP | Eleanor Williams Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295; 32202298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.125 | RBL2 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.125 | RBL2 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.125 | MCM3AP | Eleanor Williams Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295; 32202298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.124 | COG4 | Sarah Leigh reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.124 | MCM3AP | Eleanor Williams Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295; 32202298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.124 | COG4 | Sarah Leigh Tag for-review tag was added to gene: COG4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.124 | MCM3AP | Eleanor Williams Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.123 | MCM3AP | Eleanor Williams reviewed gene: MCM3AP: Rating: GREEN; Mode of pathogenicity: None; Publications: 32202298; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.123 | RBL2 | Sarah Leigh Classified gene: RBL2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.123 | RBL2 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Identified as a candidate gene in PMIDs 32105419; 9806916, with two variants in sibblings. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.123 | RBL2 | Sarah Leigh Gene: rbl2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.122 | SOX6 | Sarah Leigh Tag for-review tag was added to gene: SOX6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.122 | SOX6 | Sarah Leigh edited their review of gene: SOX6: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.122 | SOX6 | Sarah Leigh Classified gene: SOX6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.122 | SOX6 | Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM and as probable Gen2Phen gene for SOX6-related neurodevelopmental syndrome. At least 17 unrelated cases, with 14 de novo heterozygous variants, a further 2 families where the variant appeared to inherited from the affected father and a single case where the variant was found to be mosaic in the unaffected father. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.122 | SOX6 | Sarah Leigh Gene: sox6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.121 | RBL2 | Sarah Leigh Classified gene: RBL2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.121 | RBL2 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Identified as a candidate gene in PMIDs 32105419; 9806916, with two variants in sibblings. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.121 | RBL2 | Sarah Leigh Gene: rbl2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.120 | TTC5 | Sarah Leigh edited their review of gene: TTC5: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.120 | TTC5 | Sarah Leigh Classified gene: TTC5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.120 | TTC5 | Sarah Leigh Added comment: Comment on list classification: Not associated with a relevant phenotype in OMIM and as probable Gen2Phen gene for TTC5-associated neurodevelopmental disorder. At least 7 cases with biallelic variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.120 | TTC5 | Sarah Leigh Gene: ttc5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.119 | TTC5 | Sarah Leigh Tag for-review tag was added to gene: TTC5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.119 | RBL2 | Sarah Leigh Classified gene: RBL2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.119 | RBL2 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Identified as a candidate gene in PMIDs 32105419; 9806916, with two variants in sibblings. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.119 | RBL2 | Sarah Leigh Gene: rbl2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.118 | SIX5 | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.118 | SIX5 | Sarah Leigh Classified gene: SIX5 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.118 | SIX5 | Sarah Leigh Added comment: Comment on list classification: Based on expert review and lack evidence for association with intellectual disability in publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.118 | SIX5 | Sarah Leigh Gene: six5 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.117 | SKIV2L | Sarah Leigh Classified gene: SKIV2L as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.117 | SKIV2L | Sarah Leigh Added comment: Comment on list classification: Based on expert review and lack evidence for association with intellectual disability in publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.117 | SKIV2L | Sarah Leigh Gene: skiv2l has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.116 | SKIV2L | Sarah Leigh Publications for gene: SKIV2L were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.115 | SIX5 | Sarah Leigh Publications for gene: SIX5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.115 | SIX5 | Sarah Leigh Classified gene: SIX5 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.115 | SIX5 | Sarah Leigh Added comment: Comment on list classification: Based on expert review and lack evidence for association with intellectual disability in publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.115 | SIX5 | Sarah Leigh Gene: six5 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.114 | SIX1 | Sarah Leigh Publications for gene: SIX1 were set to 25529582; Version 12 ukgtn.nhs.uk | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.113 | SIX1 | Sarah Leigh Classified gene: SIX1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.113 | SIX1 | Sarah Leigh Added comment: Comment on list classification: Based on expert review and lack evidence for association with intellectual disability in publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.113 | SIX1 | Sarah Leigh Gene: six1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.112 | SIX1 | Sarah Leigh Publications for gene: SIX1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.112 | SIX1 | Sarah Leigh Classified gene: SIX1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.112 | SIX1 | Sarah Leigh Added comment: Comment on list classification: Based on expert review and lack evidence for association with intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.112 | SIX1 | Sarah Leigh Gene: six1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.111 | SLC1A1 | Sarah Leigh Publications for gene: SLC1A1 were set to 21123949; 16311588; 16311588 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.110 | SLC1A1 | Sarah Leigh Classified gene: SLC1A1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.110 | SLC1A1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in 2 unrelated cases (PMID 21123949), a SLC1A1 null mouse model with age-dependent chronic neurodegeneration (PMID 16311588), together with historic reports of intellectual disability associated with the phenotype (PMID 894411). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.110 | SLC1A1 | Sarah Leigh Gene: slc1a1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.109 | SLC1A1 | Sarah Leigh reviewed gene: SLC1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.109 | SLC1A1 | Sarah Leigh Phenotypes for gene: SLC1A1 were changed from Dicarboxylic aminoaciduria 222730 to Dicarboxylic aminoaciduria 222730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.108 | SLC1A1 | Sarah Leigh Tag for-review tag was added to gene: SLC1A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.108 | SLC1A1 | Sarah Leigh Phenotypes for gene: SLC1A1 were changed from Dicarboxylic aminoaciduria 222730 to Dicarboxylic aminoaciduria 222730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.107 | SLC1A1 | Sarah Leigh Publications for gene: SLC1A1 were set to 21123949; 21123949 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.106 | SLC1A1 | Sarah Leigh Publications for gene: SLC1A1 were set to Dicarboxylic aminoaciduria, MIM#222730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.105 | SLC1A1 | Sarah Leigh Phenotypes for gene: SLC1A1 were changed from to Dicarboxylic aminoaciduria 222730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | DMD | Sarah Leigh commented on gene: DMD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | PIGS | Sarah Leigh edited their review of gene: PIGS: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | PIGS | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | PIGS | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | PIGS | Sarah Leigh Classified gene: PIGS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | PIGS | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in at least 3 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.104 | PIGS | Sarah Leigh Gene: pigs has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.103 | PIGS | Sarah Leigh Classified gene: PIGS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.103 | PIGS | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in at least 3 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.103 | PIGS | Sarah Leigh Gene: pigs has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.103 | PIGS | Sarah Leigh Classified gene: PIGS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.103 | PIGS |
Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in at least 3 unrelated cases. THIS GENE COULD BE RATED GREEN AT THE NEXT MAJOR REVIEW |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.103 | PIGS | Sarah Leigh Gene: pigs has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.102 | PIGS | Sarah Leigh Tag for-review tag was added to gene: PIGS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.102 | PIGS | Sarah Leigh Phenotypes for gene: PIGS were changed from Glycosylphosphatidylinositol biosynthesis defect 18, MIM# 618143 to Glycosylphosphatidylinositol biosynthesis defect 18 618143 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.101 | ALG14 | Sarah Leigh commented on gene: ALG14: Have added the "for review" tag, to address the phenotypic variability of published carriers of ALG14 variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.101 | ALG14 | Sarah Leigh Classified gene: ALG14 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.101 | ALG14 | Sarah Leigh Added comment: Comment on list classification: Associated with Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 in OMIM, but not associated with phenotype in Gen2Phen. At least 6 variants reported in at least 5 cases with varying phenotypes. PMID 23404334 reports compound heterozygous (p.P65L, P.R104*) sibs, who manifested with myasthenic syndromes, but did not have intellectural disability nor seizures and were 62 and 51 years old when reported. PMID 28733338 reports two compound heterozygous (p.D74N, pV141G), (p.D74N, p.R109Q) cases and a homozygous ((p.D74N), with early and lethal neurodegeneration with myasthenic and myopathic features, but the cases died before intellectual disability was manifiest. However, seizures were evident in two compound heterozygous families. PMID 30221345 reports a homozygous splicing variant in a case with intellectual disability and seizures. Functional studies were presented showing that this variant resulting in exon skipping, however, this was not completely prenetrant as wild type protein was detected at a low level in the patient. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.101 | ALG14 | Sarah Leigh Gene: alg14 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.100 | ALG14 | Sarah Leigh Tag for-review tag was added to gene: ALG14. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.100 | CNOT3 | Sarah Leigh commented on gene: CNOT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.100 | ALG14 | Sarah Leigh Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227; Intellectual disability to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.99 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.99 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.98 | PIGK | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.98 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.97 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.96 | PIGK | Sarah Leigh Classified gene: PIGK as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.96 | PIGK | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for PIGK-associated Neurodevelopmental Syndrome. At least 10 variants reported in at least 9 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.96 | PIGK | Sarah Leigh Gene: pigk has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.95 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.95 | PIGK | Sarah Leigh Classified gene: PIGK as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.95 | PIGK | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for PIGK-associated Neurodevelopmental Syndrome. At least 10 variants reported in at least 9 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.95 | PIGK | Sarah Leigh Gene: pigk has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.94 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.93 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.92 | PIGK | Sarah Leigh Phenotypes for gene: PIGK were changed from Intellectual disability; seizures; cerebellar atrophy to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.91 | SCAF4 | Eleanor Williams Tag watchlist tag was added to gene: SCAF4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.91 | SATB1 | Eleanor Williams Tag watchlist tag was added to gene: SATB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.91 | WNT1 | Catherine Snow Classified gene: WNT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.91 | WNT1 | Catherine Snow Added comment: Comment on list classification: Identified by expert review from Zornitza Stark, sufficient number of unrelated patients for WNT1 to be classified as Green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.91 | WNT1 | Catherine Snow Gene: wnt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.90 | SCAF4 |
Eleanor Williams changed review comment from: ESHG2020 - C02.1 - SCAF4 loss of function in humans and Drosophila implicates mRNA transcriptional termination in neurodevelopmental disorders - Fliedner et al - report 9 unrelated patients with likely pathogenic variants in SCAF4 and mild developmental delay and intellectual disability. 8 de novo. 1 inherited. Seizures, skeletal, renal and cardiac anomalies were also seen. Sources: Literature; to: Conference talk/abstract from ESHG2020 - C02.1 - SCAF4 loss of function in humans and Drosophila implicates mRNA transcriptional termination in neurodevelopmental disorders - Fliedner et al - report 9 unrelated patients with likely pathogenic variants in SCAF4 and mild developmental delay and intellectual disability. 8 de novo. 1 inherited. Seizures, skeletal, renal and cardiac anomalies were also seen. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.90 | SCAF4 |
Eleanor Williams gene: SCAF4 was added gene: SCAF4 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added comment: ESHG2020 - C02.1 - SCAF4 loss of function in humans and Drosophila implicates mRNA transcriptional termination in neurodevelopmental disorders - Fliedner et al - report 9 unrelated patients with likely pathogenic variants in SCAF4 and mild developmental delay and intellectual disability. 8 de novo. 1 inherited. Seizures, skeletal, renal and cardiac anomalies were also seen. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.89 | CDC42BPB | Sarah Leigh Classified gene: CDC42BPB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.89 | CDC42BPB | Sarah Leigh Gene: cdc42bpb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh changed review comment from: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo.; to: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. Intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo. However, only two of these cases did not have additional genetic changes reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh Classified gene: CDC42BPB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh Gene: cdc42bpb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.87 | DSCR3 |
Zornitza Stark gene: DSCR3 was added gene: DSCR3 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DSCR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DSCR3 were set to 31845315 Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet Review for gene: DSCR3 was set to RED Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.87 | CDC42BPB | Sarah Leigh Added comment: Comment on phenotypes: CDC42BPB-related Neurodevelopmental Disorder is assigned by Gen2Phen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.87 | CDC42BPB | Sarah Leigh Phenotypes for gene: CDC42BPB were changed from Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality to CDC42BPB-related Neurodevelopmental Disorder; Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.86 | NFASC | Sarah Leigh Publications for gene: NFASC were set to 28940097; 30124836; 30850329 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.85 | TMX2 | Sarah Leigh Publications for gene: TMX2 were set to 31586943; 31270415 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.84 | C16orf62 | Sarah Leigh changed review comment from: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).; to: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 31712251). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.84 | C16orf62 | Sarah Leigh Publications for gene: C16orf62 were set to 25434475 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.83 | SRCAP | Eleanor Williams commented on gene: SRCAP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.83 | SATB1 |
Eleanor Williams changed review comment from: Conference talk/abstract from ESHG 2020 - Mutation-specific pathophysiological mechanisms in a new SATB1-associated neurodevelopmental disorder - Den Hoed et al - report f26 individuals with SATB1 variants, 17 of which have missense variants and 9 have truncating variants. 21 of 26 variants (80%) were confirmed to be de novo in origin. Patients showed a broad phenotypic spectrum, including ID and/or neurodevelopmental delay, epilepsy, dental abnormalities and aspecific brain MRI findings. Additionally, patients with missense variants are more severely affected than those with truncating variants. No peer reviewed publication was found in PubMed relating to these results so recommend Amber rating for now. Sources: Other; to: Conference talk/abstract from ESHG 2020 - Mutation-specific pathophysiological mechanisms in a new SATB1-associated neurodevelopmental disorder - Den Hoed et al - report 26 individuals with SATB1 variants, 17 of which have missense variants and 9 have truncating variants. 21 of 26 variants (80%) were confirmed to be de novo in origin. Patients showed a broad phenotypic spectrum, including ID and/or neurodevelopmental delay, epilepsy, dental abnormalities and aspecific brain MRI findings. Additionally, patients with missense variants are more severely affected than those with truncating variants. No peer reviewed publication was found in PubMed relating to these results so recommend Amber rating for now. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.83 | SATB1 |
Eleanor Williams gene: SATB1 was added gene: SATB1 was added to Intellectual disability. Sources: Other Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SATB1 were set to intellectual disability Review for gene: SATB1 was set to AMBER Added comment: Conference talk/abstract from ESHG 2020 - Mutation-specific pathophysiological mechanisms in a new SATB1-associated neurodevelopmental disorder - Den Hoed et al - report f26 individuals with SATB1 variants, 17 of which have missense variants and 9 have truncating variants. 21 of 26 variants (80%) were confirmed to be de novo in origin. Patients showed a broad phenotypic spectrum, including ID and/or neurodevelopmental delay, epilepsy, dental abnormalities and aspecific brain MRI findings. Additionally, patients with missense variants are more severely affected than those with truncating variants. No peer reviewed publication was found in PubMed relating to these results so recommend Amber rating for now. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.82 | C16orf62 | Sarah Leigh Classified gene: C16orf62 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.82 | C16orf62 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.82 | C16orf62 | Sarah Leigh Gene: c16orf62 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.81 | C16orf62 | Sarah Leigh commented on gene: C16orf62: The HGNC approved name for this gene is: VPS35 endosomal protein sorting factor like (VPS35L) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.81 | C16orf62 | Sarah Leigh Tag new-gene-name tag was added to gene: C16orf62. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.81 | C16orf62 |
Sarah Leigh gene: C16orf62 was added gene: C16orf62 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C16orf62 were set to 25434475 Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome Review for gene: C16orf62 was set to AMBER Added comment: Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | RBL2 |
Zornitza Stark gene: RBL2 was added gene: RBL2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBL2 were set to 32105419; 9806916 Phenotypes for gene: RBL2 were set to intellectual diability Review for gene: RBL2 was set to RED Added comment: Single family reported with pair of affected siblings. Supportive mouse model. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | OTUD7A |
Zornitza Stark gene: OTUD7A was added gene: OTUD7A was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074 Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, intellectual disability, no OMIM# yet Review for gene: OTUD7A was set to RED Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy reported. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies. Mouse model and other data support the role of this gene in neurodevelopmental phenotypes but nevertheless, single family to date. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | COG4 | Zornitza Stark edited their review of gene: COG4: Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | COG4 | Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | TTC5 | Zornitza Stark reviewed gene: TTC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29302074, 32439809; Phenotypes: Central hypotonia, Global developmental delay, Intellectual disability, Abnormality of nervous system morphology, Microcephaly, Abnormality of the face, Behavioral abnormality, Abnormality of the genitourinary system; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | HIST1H4J |
Zornitza Stark gene: HIST1H4J was added gene: HIST1H4J was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HIST1H4J were set to 31804630 Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features Review for gene: HIST1H4J was set to AMBER Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to HIST1H4C phenotype Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | SNX27 | Sarah Leigh Classified gene: SNX27 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | SNX27 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM (lasted edited on 05/23/2012) or in Gen2Phen. However, five variants in three unrelated cases, together with supportive functional studies and mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.80 | SNX27 | Sarah Leigh Gene: snx27 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.79 | SOX6 |
Zornitza Stark gene: SOX6 was added gene: SOX6 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOX6 were set to 32442410 Phenotypes for gene: SOX6 were set to intellectual diability; ADHD; Craniosynostosis; Osteochondromas Review for gene: SOX6 was set to GREEN gene: SOX6 was marked as current diagnostic Added comment: 19 individuals from 17 families with a neurodevelopmental syndrome reported. 6 LoF, 4 missense, and 6 intragenic deletion variants identified. ID ranged from mild to severe. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.79 | SLC5A6 | Sarah Leigh Classified gene: SLC5A6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.79 | SLC5A6 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene for SLC5A6-related Neurodevelopmental Disorder. At least 5 variants published in three unrelated famililies (4 cases total) with SLC5A6-related Neurodevelopmental Disorder, together with supportive functional studies (PMID 29669219; 23104561). One of the cases had mixed semiology seizures including focal dyscognitive, absence, tonic spasms and generalised convulsive seizures with electrographic features of encephalopathy with generalised and independent multifocal spike-wave discharges (PMID 31754459), another case had brain, immune, bone and intestinal dysfunction (PMID 27904971) and the third had metabolic dysfunction mimicking biotinidase deficiency (PMID 31392107). This condition could be treated with biotin supplementation and introduction of pantothenic acid supplementation (PMID 31392107). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.79 | SLC5A6 | Sarah Leigh Gene: slc5a6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | CXorf56 | Sarah Leigh Tag Skewed X-inactivation tag was added to gene: CXorf56. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | RNF113A | Sarah Leigh Tag Skewed X-inactivation tag was added to gene: RNF113A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | PIGA | Sarah Leigh Tag Skewed X-inactivation tag was added to gene: PIGA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | DMD | Sarah Leigh Tag Skewed X-inactivation tag was added to gene: DMD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | TTC5 |
Konstantinos Varvagiannis gene: TTC5 was added gene: TTC5 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC5 were set to 29302074; 32439809 Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system Penetrance for gene: TTC5 were set to Complete Review for gene: TTC5 was set to GREEN Added comment: Hu et al (2019 - PMID: 29302074) reported briefly on 3 individuals from 2 consanguineous families (from Turkey and Iran) with biallelic TTC5 variants. Features included DD (3/3), ID (severe in 2/2 with relevant age), microcephaly (3/3), brain abnormalities, etc. A nonsense and a variant affecting splice site were identified by WES/WGS. --- In a recent report, Rasheed et al (2020 - PMID: 32439809) report on the phenotype of 8 individuals - belonging to 5 consanguineous families - all 8 harboring homozygous TTC5 mutations. Frequent features included hypotonia (6/8), motor and speech delay, moderate to severe ID (10/10 of relevant age - inclusion of less severely affected subjects was not considered by study design), brain MRI abnormalities (8/8). Other findings included microcephaly in some (6/11), behavioral abnormalities in few (autistic behavior in 2/8, aggression in 2/8), genitourinary anomalies (2/8), seizures (1/11). Facial phenotype incl. thin V-shaped upper lip, low-set ears (in most) and/or additional features. TTC5 encodes a 440 aa protein, functioning as a scaffold to stabilise p300-JMY interactions. Apart from this role in nucleus, it has functions in the cytoplasm (inhibiting actin nucleataion, autophagosome formation, etc). The gene has ubiquitous expression, highest in brain. All variants were identified following WES - as the best candidates - in affected individuals with compatible Sanger studies in all affected family members and carrier parents. 2 missense and 2 nonsense variants were identified with the 2 missense SNVs localizing within TPR domains. qRT-PCR studies for a nonsense variant localizing 19 nt before the last exon, revealed fourfold decreased expression in affected individuals compared to carriers. Families from Egypt shared a homozygous ~6.3 Mb haplotype block spanning TTC5, suggesting that p.(Arg263Ter) is likely a founder mutation. The authors underscore some phenotypic (though not facial) similarities with Rubinstein-Taybi syndrome 2 due to EP300 mutations (in line with the role of TTC5). Biallelic variants in genes encoding other members of the TTC family (containing a TPR motif), e.g. TTC8 or TTC15 cause disorders with neurologic manifestations (and DD/ID). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | AGMO | Rebecca Foulger changed review comment from: Comment on list classification: Gene was added to the panel and rated Green by Zornitza Stark. One family presented in PMID:27000257, and 2 compound het cases in PMID:31555905 (though there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant). Functional data shows decreased enzyme activity of the variants. Although there are 3 cases, the phenotype is variable between patients (ID/DD vs regression). Therefore, rated as Amber awaiting further cases and clinical opinion.; to: Comment on list classification: Gene was added to the panel and rated Green by Zornitza Stark. One family presented in PMID:27000257, and 2 compound het cases in PMID:31555905 (though there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant). Functional data shows decreased enzyme activity of the variants. Although there are 3 cases, the phenotype is variable between patients (ID/DD vs regression) and therefore this is borderline. Therefore, rated as Amber awaiting further cases and clinical opinion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | AGMO | Rebecca Foulger changed review comment from: Comment on list classification: Gene was added to the panel and rated Green by Zornitza Stark. One homozygous case presented in PMID:27000257, and 2 compound het cases in PMID:31555905 (though there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant). Functional data shows decreased enzyme activity of the variants. Although there are 3 cases, the phenotype is variable between patients (ID/DD vs regression). Therefore, rated as Amber awaiting further cases and clinical opinion.; to: Comment on list classification: Gene was added to the panel and rated Green by Zornitza Stark. One family presented in PMID:27000257, and 2 compound het cases in PMID:31555905 (though there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant). Functional data shows decreased enzyme activity of the variants. Although there are 3 cases, the phenotype is variable between patients (ID/DD vs regression). Therefore, rated as Amber awaiting further cases and clinical opinion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | AGMO | Rebecca Foulger Classified gene: AGMO as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | AGMO | Rebecca Foulger Added comment: Comment on list classification: Gene was added to the panel and rated Green by Zornitza Stark. One homozygous case presented in PMID:27000257, and 2 compound het cases in PMID:31555905 (though there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant). Functional data shows decreased enzyme activity of the variants. Although there are 3 cases, the phenotype is variable between patients (ID/DD vs regression). Therefore, rated as Amber awaiting further cases and clinical opinion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.78 | AGMO | Rebecca Foulger Gene: agmo has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.77 | AGMO | Rebecca Foulger changed review comment from: PMID:27000257 (2016) Alrayes et al., 2016 enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. They identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene in 2 brothers. Population screening of 178 ethnically matched control chromosomes and consultation of the ExAC database confirmed that this variant was not present outside the family. Epilepsy is not mentioned amongst their phenotypes.; to: PMID:27000257 (2016) Alrayes et al., 2016 enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. They identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene in 2 brothers. Population screening of 178 ethnically matched control chromosomes and consultation of the ExAC database confirmed that this variant was not present outside the family. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.77 | AGMO | Rebecca Foulger changed review comment from: PMID:31555905. Okur et al., report rare nonsense in-frame deletion and missense compound heterozygous variants in AGMO in 2 unrelated individuals (8 year old European girl, and 4-year old Ashkenazi Jewish boy). They demonstrated significantly diminished enzyme activity for all disease-associated variants. The girl harboured variants p.Trp130Ter & p.Gly238Cys. The boy harboured variants p.Gly144Arg and p.Tyr236del. Note that there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant. Table 1 also mentions MTHFR C677T homozygous for the boy, but this is not referred to within the text. ID/DD (and seizures) was reported in the girl. The boy showed normal development to begin, but began to regress age 3.5 years.; to: PMID:31555905. Okur et al., report rare nonsense in-frame deletion and missense compound heterozygous variants in AGMO in 2 unrelated individuals (8 year old European girl, and 4-year old Ashkenazi Jewish boy). They demonstrated significantly diminished enzyme activity for all disease-associated variants. The girl harboured variants p.Trp130Ter & p.Gly238Cys. The boy harboured variants p.Gly144Arg and p.Tyr236del. Note that there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant. Table 1 also mentions MTHFR C677T homozygous for the boy, but this is not referred to within the text. ID/DD (and seizures) were reported in the girl. The boy showed normal development to begin, but began to regress age 3.5 years. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.77 | AGMO | Rebecca Foulger Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to microcephaly; intellectual disability; epilepsy; developmental delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.77 | AGMO | Rebecca Foulger Publications for gene: AGMO were set to 31555905 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.76 | AGMO | Rebecca Foulger commented on gene: AGMO: PMID:31555905. Okur et al., report rare nonsense in-frame deletion and missense compound heterozygous variants in AGMO in 2 unrelated individuals (8 year old European girl, and 4-year old Ashkenazi Jewish boy). They demonstrated significantly diminished enzyme activity for all disease-associated variants. The girl harboured variants p.Trp130Ter & p.Gly238Cys. The boy harboured variants p.Gly144Arg and p.Tyr236del. Note that there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant. Table 1 also mentions MTHFR C677T homozygous for the boy, but this is not referred to within the text. ID/DD (and seizures) was reported in the girl. The boy showed normal development to begin, but began to regress age 3.5 years. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.76 | AGMO | Rebecca Foulger commented on gene: AGMO | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.76 | KAT8 | Rebecca Foulger Tag missense tag was added to gene: KAT8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.76 | KAT8 | Rebecca Foulger commented on gene: KAT8: Added 'missense' tag because all de novo variants in PMID:31794431 are missense. Note that for the biallelic case in the same paper, one of the variants is nonsense. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.76 | KAT8 | Rebecca Foulger Mode of pathogenicity for gene: KAT8 was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.75 | KAT8 | Rebecca Foulger Added comment: Comment on mode of inheritance: Individual T9 inherited biallelc variants from her asymptomatic parents. Her sister carried 1 variant and showed no obvious symptoms. This may be due to incomplete genetic penetrance, or the two variants act differently from the de novo heterozygous variants identified. This is the only example of biallelic inheritance, so have set MOI to 'monoallelic' until more cases are identified. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.75 | KAT8 | Rebecca Foulger Mode of inheritance for gene: KAT8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.74 | KAT8 | Rebecca Foulger Classified gene: KAT8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.74 | KAT8 | Rebecca Foulger Added comment: Comment on list classification: Gene was added to the panel and rated Green by Konstantinos Varvagiannis, and subsequently reviewed Green by Zornitza Stark. Not yet associated with a disorder in OMIM or G2P. All cases come from PMID:31794431 (Li et al.2019) who report 8 unrelated individuals with heterozygous de novo pathogenic KAT8 variants (T1,T2,T3 had the same variant), plus one individual compound het for a nonsense and a missense variant (p.Lys175* and p.Arg325Cys). All individuals had DD and/or ID (Supplementary materials). Knockout mice failed to thrive, and showed early lethality and cerebral hypoplasia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.74 | KAT8 | Rebecca Foulger Gene: kat8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.73 | CXorf56 | Rebecca Foulger changed review comment from: Comment on mode of inheritance: OMIM records XL inheritance for MIM:301013 with X-linked inactivation. In PMID:29374277 carrier females had skewed X-inactivation whereas the affected female did not. In PMID:31822863 X-linked skewing was seen in both affected females and the unaffected carrier.; to: Comment on mode of inheritance: OMIM records XL inheritance for MIM:301013 noting X-linked inactivation in the comments. In PMID:29374277 carrier females had skewed X-inactivation whereas the affected female did not. In PMID:31822863 X-linked skewing was seen in both affected females and the unaffected carrier. Have set MOI to XLD for now, to capture affected females and males. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.73 | CXorf56 | Rebecca Foulger Classified gene: CXorf56 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.73 | CXorf56 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green. Gene was added to panel by Konstantinos Varvagiannis, with a subsequent Green review by Zornitza Stark. Sufficient cases in PMIDs:29374277 and 31822863. The reported pattern of X-inactivation differs between the papers, but sufficient cases and relevant phenotype for inclusion on the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.73 | CXorf56 | Rebecca Foulger Gene: cxorf56 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.72 | CXorf56 | Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM records XL inheritance for MIM:301013 with X-linked inactivation. In PMID:29374277 carrier females had skewed X-inactivation whereas the affected female did not. In PMID:31822863 X-linked skewing was seen in both affected females and the unaffected carrier. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.72 | CXorf56 | Rebecca Foulger Mode of inheritance for gene: CXorf56 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 v3.71 | CXorf56 | Rebecca Foulger commented on gene: CXorf56: PMID:31822863. Rocha et al., 2019 report on 9 affected individuals (3 unrelated families) with mild to severe ID and variants in CXorf56. In comparison to PMID:29374277, X-linked skewing was seen in both affected females and the unaffected carrier had complete inactivation of the carrier X-chromosome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.71 | CXorf56 | Rebecca Foulger commented on gene: CXorf56 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.71 | UGP2 | Rebecca Foulger Classified gene: UGP2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.71 | UGP2 | Rebecca Foulger Added comment: Comment on list classification: Gene added to panel and rated Green by Konstantinos Varvagiannis. Subsequently reviewed Green by Zornitza Stark. Sufficient evidence and appropriate phenotype (DD seen in all patients in PMID:31820119) for inclusion on panel: 20 patients from 13 unrelated families all with the same variant identified in PMID:31820119 (2019 publication). Therefore updated rating from Grey to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.71 | UGP2 | Rebecca Foulger Gene: ugp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.70 | UGP2 | Rebecca Foulger Phenotypes for gene: UGP2 were changed from Seizures; Global developmental delay; Intellectual disability; Feeding difficulties; Abnormality of vision; Abnormality of the face to Epileptic encephalopathy, early infantile, 83, 618744; Global developmental delay; Intellectual disability; Feeding difficulties; Abnormality of vision; Abnormality of the face | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.69 | TRAPPC4 | Rebecca Foulger Classified gene: TRAPPC4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.69 | TRAPPC4 | Rebecca Foulger Added comment: Comment on list classification: Added to panel and rated Green by Konstantinos Varvagiannis. Subsequent Green review by Zornitza Stark. Updated rating from Grey to Green: 7 children from 3 unrelated families with MIM:618741 reported by, Van Bergen et al. (2020) with a recurring homozygous splice site variant in TRAPPC4 resulting in a splice site alteration, the skipping of exon 3, a frameshift, and premature termination (Leu120AspfsTer9). The variant segregated within the disorder within the families and was only found in heterozygous state in gnomAD. Appropriate phenotype and cases just reach threshold for inclusion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.69 | TRAPPC4 | Rebecca Foulger Gene: trappc4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.68 | TRAPPC4 | Rebecca Foulger Phenotypes for gene: TRAPPC4 were changed from Feeding difficulties; Progressive microcephaly; Intellectual disability; Seizures; Spastic tetraparesis; Abnormality of the face; Scoliosis; Cortical visual impairment; Hearing impairment to Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, 618741 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.67 | WDR45B | Rebecca Foulger Phenotypes for gene: WDR45B were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.67 | WDR45B | Rebecca Foulger Publications for gene: WDR45B were set to 21937992; 28503735 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.66 | ALKBH8 | Rebecca Foulger Classified gene: ALKBH8 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.66 | ALKBH8 | Rebecca Foulger Added comment: Comment on list classification: Demoted from Green to Amber based on advice from the Genomics England Clinical Team. In email correspondence, Helen Brittain notes that this is a borderline gene in terms of evidence (two families, 6/7 individuals with seizures and not particularly extensive functional / supportive information). Zornitza's review on the Genetic Epilepsy Syndromes panel focuses on the differing ratings of ALKBH8 on the ID (Green) and Epilepsy (Amber) panels. Based on borderline evidence, I have demoted ALKBH8 to Amber on the ID panel to be consistent with the GLH consensus on the Epilepsy panel (R59 #402). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.66 | ALKBH8 | Rebecca Foulger Gene: alkbh8 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.65 | PTRHD1 | Helen Brittain Marked gene: PTRHD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.65 | PTRHD1 | Helen Brittain Added comment: Comment when marking as ready: Further case from personal correspondence. Considered sufficient for a green rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.65 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.65 | PTRHD1 | Helen Brittain Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism, Intellectual disability; Parkinsonism to Intellectual disability; Parkinsonism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.64 | PTRHD1 | Helen Brittain Classified gene: PTRHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.64 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.63 | PTRHD1 | Helen Brittain Tag watchlist was removed from gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.63 | PTRHD1 | Helen Brittain Classified gene: PTRHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.63 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.63 | PTRHD1 | Helen Brittain Classified gene: PTRHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.63 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.62 | PTRHD1 | Helen Brittain reviewed gene: PTRHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.62 | TMX2 | Eleanor Williams Phenotypes for gene: TMX2 were changed from Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormal cortical gyration to Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormal cortical gyration; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, 618730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.61 | SMARCD1 | Eleanor Williams Phenotypes for gene: SMARCD1 were changed from Generalized hypotonia; Feeding difficulties; Global developmental delay; Intellectual disability; Abnormality of the hand; Abnormality of the foot to Generalized hypotonia; Feeding difficulties; Global developmental delay; Intellectual disability; Abnormality of the hand; Abnormality of the foot; Coffin-Siris syndrome 11, 618779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.60 | NKAP | Eleanor Williams Phenotypes for gene: NKAP were changed from Global developmental delay; Intellectual disability to Global developmental delay; Intellectual disability; Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type #301039 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.59 | DLG4 | Eleanor Williams Phenotypes for gene: DLG4 were changed from Intellectual disability; Marfanoid habitus to Intellectual disability; Marfanoid habitus; Intellectual developmental disorder 62 #618793 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.58 | CDK8 | Eleanor Williams Phenotypes for gene: CDK8 were changed from Generalized hypotonia; Feeding difficulties; Global developmental delay; Intellectual disability; Behavioral abnormality; Abnormality of cardiovascular system morphology; Hearing impairment; Abnormality of vision; Anorectal anomaly; Seizures to Generalized hypotonia; Feeding difficulties; Global developmental delay; Intellectual disability; Behavioral abnormality; Abnormality of cardiovascular system morphology; Hearing impairment; Abnormality of vision; Anorectal anomaly; Seizures; Intellectual developmental disorder with hypotonia and behavioral abnormalities #618748 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.57 | PCYT2 | Rebecca Foulger Phenotypes for gene: PCYT2 were changed from Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Spastic tetraparesis; Cerebral atrophy; Cerebellar atrophy to Spastic paraplegia 82, autosomal recessive, 618770; Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Spastic tetraparesis; Cerebral atrophy; Cerebellar atrophy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.56 | EXT2 | Rebecca Foulger Classified gene: EXT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.56 | EXT2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Sufficient cases to support causation of MIM:616682, of which ID is a prominent phenotype. Note that I have updated the Mode of Inheritance from AD to AR to match MIM:616682 (and the Genetic epilepsy syndromes panel, #402). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.56 | EXT2 | Rebecca Foulger Gene: ext2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.55 | EXT2 | Rebecca Foulger changed review comment from: PMID:30288735. In 2 siblings with MIM:616682, Gentile et al identified compound het missense variants in EXT2, which segregated with the disorder (D227N and Y608C). The D227N vairant contributes to exostosis (inherited from the mother who had a family history of exostosis).; to: PMID:30288735. In 2 siblings with MIM:616682, Gentile et al identified compound het missense variants in EXT2, which segregated with the disorder (D227N and Y608C). The D227N variant contributes to exostosis (inherited from the mother who had a family history of exostosis). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.55 | EXT2 | Rebecca Foulger commented on gene: EXT2: PMID:30288735. In 2 siblings with MIM:616682, Gentile et al identified compound het missense variants in EXT2, which segregated with the disorder (D227N and Y608C). The D227N vairant contributes to exostosis (inherited from the mother who had a family history of exostosis). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.55 | EXT2 | Rebecca Foulger commented on gene: EXT2: PMID:30997052. In a 14 year old girl, Gupta et al. (2019) identified compound het missense variants in the EXT2 gene (V373D and T672M), which segregated with the disorder in the family. The patient also carried a maternal heterozygous variant (R454C) in NDST1. She had developmental delay, autism and epilepsy amongst her phenotypes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.55 | EXT2 | Rebecca Foulger commented on gene: EXT2: PMID:30075207. In 2 brothers, born of consanguineous Syrian parents, with MIM:616682 El-Bazzal et al. (2019) identified a homozygous missense mutation in the EXT2 gene (p.Ser4Leu). Psychomotor delay was noted for both at the age of 3 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.55 | EXT2 | Rebecca Foulger commented on gene: EXT2: PMID:26246518: In 4 siblings, born of consanguineous parents in the Old Order Mennonite community, with seizures, scoliosis, and macrocephaly/microcephaly syndrome (MIM:616682), Farhan et al. (2015) identified homozygosity for 2 missense mutations in EXT2 (M87R and R95C). All siblings had moderate ID and a seizure disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.55 | EXT2 | Rebecca Foulger Phenotypes for gene: EXT2 were changed from Seizures, scoliosis, and macrocephaly syndrome, 616682 to Seizures, scoliosis, and macrocephaly syndrome, 616682; autosomal recessive EXT2-related syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.54 | EXT2 | Rebecca Foulger Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.54 | EXT2 | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from MONOALLELIC to BIALLELIC. EXT2 is associated with 2 different disorders: Seizures, scoliosis, and macrocephaly syndrome, 616682 (AR) and Exostoses, multiple, type 2, 133701 (AD). MIM:616682 is relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.54 | EXT2 | Rebecca Foulger Mode of inheritance for gene: EXT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.53 | EXT2 | Rebecca Foulger Publications for gene: EXT2 were set to 25529582; 26246518; 30997052; 30288735 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.52 | EXT2 | Rebecca Foulger Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2, 133701 to Seizures, scoliosis, and macrocephaly syndrome, 616682 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.51 | EXT2 | Rebecca Foulger Publications for gene: EXT2 were set to 25529582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.51 | EXT2 | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from MONOALLELIC to BIALLELIC. EXT2 is associated with 2 different disorders: Seizures, scoliosis, and macrocephaly syndrome, 616682 (AR) and Exostoses, multiple, type 2, 133701 (AD). MIM:616682 is relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.51 | EXT2 | Rebecca Foulger Mode of inheritance for gene: EXT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.50 | EXT2 | Rebecca Foulger Mode of inheritance for gene: EXT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.49 | EXT2 | Rebecca Foulger Publications for gene: EXT2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.48 | WASF1 | Rebecca Foulger Phenotypes for gene: WASF1 were changed from ID associated with autistic features, seizures, and developmental delay; intellectual disability to Neurodevelopmental disorder with absent language and variable seizures, 618707; ID associated with autistic features, seizures, and developmental delay; intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.47 | POU3F3 | Rebecca Foulger Phenotypes for gene: POU3F3 were changed from Generalized hypotonia; Delayed speech and language development; Global developmental delay; Intellectual disability; Autistic behavior to Snijders Blok-Fisher syndrome, 618604; Generalized hypotonia; Delayed speech and language development; Global developmental delay; Intellectual disability; Autistic behavior | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.46 | POLR2A | Rebecca Foulger Phenotypes for gene: POLR2A were changed from Global developmental delay; Generalized hypotonia; Feeding difficulties to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, 618603; Global developmental delay; Generalized hypotonia; Feeding difficulties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.45 | PHF21A | Rebecca Foulger Added comment: Comment on phenotypes: Potocki-Shaffer syndrome (MIM:601224) is a contiguous gene deletion syndrome involving genes on chromosome 11p11.2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.45 | PHF21A | Rebecca Foulger Phenotypes for gene: PHF21A were changed from Potocki-Shaffer syndrome, 601224; PSS; Intellectual disability; Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, 618725 to Potocki-Shaffer syndrome, 601224; PSS; Intellectual disability; Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, 618725 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.44 | PHF21A | Rebecca Foulger Phenotypes for gene: PHF21A were changed from Potocki-Shaffer syndrome, 601224; PSS; Intellectual disability to Potocki-Shaffer syndrome, 601224; PSS; Intellectual disability; Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, 618725 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.43 | MSL3 | Rebecca Foulger Phenotypes for gene: MSL3 were changed from Muscular hypotonia; Feeding difficulties; Neurodevelopmental delay; Intellectual disability; no OMIM number to Muscular hypotonia; Feeding difficulties; Neurodevelopmental delay; Intellectual disability; Basilicata-Akhtar syndrome, 301032 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.42 | CNOT3 | Rebecca Foulger commented on gene: CNOT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.42 | CNOT3 | Rebecca Foulger Mode of inheritance for gene: CNOT3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.41 | CNOT3 | Rebecca Foulger Publications for gene: CNOT3 were set to 25529582; 28135719 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.40 | CNOT3 | Rebecca Foulger Phenotypes for gene: CNOT3 were changed from CNOT3 syndrome; intellectual disability, global developmental delay to CNOT3 syndrome; intellectual disability, global developmental delay; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, 618672 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.39 | NR4A2 |
Konstantinos Varvagiannis edited their review of gene: NR4A2: Added comment: Singh et al (2020 - https://doi.org/10.1038/s41436-020-0815-4) provide details on the phenotype of 9 unrelated individuals with NR4A2 pathogenic variants (in almost all cases de novo). Features included hypotonia (in 6/9), DD (9/9), varying levels of ID (mild to severe in 8/8 for whom this information was available), seizures (6/9 - variable epilepsy phenotypes), behavioral problems (5/9 - with autism reported for one). Less frequent features incl. hypermobility (in 3), ataxia/movement disorder (in 3). 8 total pLoF and missense variants were identified as de novo events following trio exome sequencing with Sanger validation (7/8 variants). For 1(/8) individual with a stopgain variant, a single parental sample was available. A 9th individual was found to harbor a ~3.7 Mb 2q deletion spanning also other genes (which might also contribute to his phenotype of epilepsy). Only the effect of a variant affecting the splice-acceptor site was studied (c.865-1_865delGCinsAAAAAGGAGT - NM_006186.3) with RT-PCR demonstrating an out-of-frame skipping of exon 4. Another variant (NM_006186.3:c.325dup) found in a subject with DD, ID and epilepsy had also previously been reported in another individual with similar phenotype of epilepsy and ID (Ramos et al - PMID: 31428396 - the variant was de novo with other causes for his phenotype excluded). As discussed by Singh et al, NR4A2 encodes a steroid-thyroid-retinoid receptor which acts as a nuclear receptor transcription factor. The authors summarize previous reports on NR4A2 haploinsufficiency (NR4A2 has a pLI of 1 and HI score of 1.28% - Z-score is 2.24). The authors comment on mouse models suggesting a role of NR4A2 for dopaminergic neurons, and provide plausible explanations for the phenotype of ID/seizures.; Changed publications: https://doi.org/10.1038/s41436-020-0815-4, 31428396, 29770430, 30504930, 28544326, 27569545, 23554088, 28135719, 27479843, 25363768; Changed phenotypes: Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.39 | CUL3 | Konstantinos Varvagiannis reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32341456; Phenotypes: Global developmental delay, Intellectual disability, Seizures, Abnormality of cardiovascular system morphology, Abnormality of the palate, Pseudohypoaldosteronism, type IIE - MIM #614496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.39 | ATP1A2 | Rebecca Foulger Phenotypes for gene: ATP1A2 were changed from Migraine, familial hemiplegic, 2 602481 to Migraine, familial hemiplegic, 2 602481; Alternating hemiplegia of childhood 1, 104290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.38 | ALG9 | Rebecca Foulger Classified gene: ALG9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.38 | ALG9 | Rebecca Foulger Added comment: Comment on list classification: As highlighted by Zornitza Stark, since the last curation review, a number of papers have been published on the ALG9 phenotype, including PMID:26453364 and PMID:28932688 who review the literature and report additional cases. At least 6-7 (of 10/11) patients have developmental delay. Therefore sufficient cases to support causation and have updated rating from Red to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.38 | ALG9 | Rebecca Foulger Gene: alg9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.37 | ALG9 | Rebecca Foulger Phenotypes for gene: ALG9 were changed from Congenital disorder of glycosylation, type Il 608776; Gillessen-Kaesbach-Nishimura syndrome 263210 to Developmental delay; Congenital disorder of glycosylation, type Il 608776; Gillessen-Kaesbach-Nishimura syndrome 263210 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.36 | ALG9 | Rebecca Foulger commented on gene: ALG9: PMID:28932688. Davis et al., 2017 review the literature for ALG9:CDG cases. They summarise 10 patients from 6 different families with one of four ALG9 variants (including the 4 new patients reported by PMID:26453364). They also report an additional patient with ALG9-CDH with a milder phenotype. Prenatally, dysmorphic features, renal cysts and cardiac malformations were detected. She had seizures and developmental delay. She had a homozygous variant in ALG9: p.Tyr287Cys. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.36 | ALG9 | Rebecca Foulger changed review comment from: PMID:26453364. AlSubhi et al., 2016 summarise 6 patients with ALG9-CDG from the literature and report 4 additional patients from a large consanguineous family. 6/10 patients had developmental disability including the index patient (IV:5), a6 year old girl with global DD, skeletal dysplasia, epilepsy, facial dysmorphisms amongst her phenotypes. The three affected cousins had similar phenotypes.; to: PMID:26453364. AlSubhi et al., 2016 summarise 6 patients with ALG9-CDG from the literature and report 4 additional patients from a large consanguineous family. 6/10 patients had developmental disability including the index patient (IV:5), a 6 year old girl with global DD, skeletal dysplasia, epilepsy, facial dysmorphisms amongst her phenotypes. The three affected cousins had similar phenotypes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.36 | ALG9 | Rebecca Foulger Publications for gene: ALG9 were set to 15945070; 15148656 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | ALG9 | Rebecca Foulger commented on gene: ALG9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | WDR34 | Catherine Snow Tag new-gene-name tag was added to gene: WDR34. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | WDR34 | Catherine Snow commented on gene: WDR34 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | WDR60 | Catherine Snow Tag new-gene-name tag was added to gene: WDR60. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | WDR60 | Catherine Snow commented on gene: WDR60 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | UGDH |
Konstantinos Varvagiannis gene: UGDH was added gene: UGDH was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGDH were set to 32001716 Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792 Penetrance for gene: UGDH were set to Complete Review for gene: UGDH was set to GREEN Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode. UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM]. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate). Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | YIF1B |
Konstantinos Varvagiannis gene: YIF1B was added gene: YIF1B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to 32006098 Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement Penetrance for gene: YIF1B were set to Complete Review for gene: YIF1B was set to GREEN Added comment: AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants. Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants. YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. YIF1B encodes an intracellular transmembrane protein. It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031). Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | SPTBN4 |
Konstantinos Varvagiannis gene: SPTBN4 was added gene: SPTBN4 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SPTBN4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPTBN4 were set to 28540413; 28940097; 29861105; 31230720; 31857255 Phenotypes for gene: SPTBN4 were set to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 Penetrance for gene: SPTBN4 were set to Complete Review for gene: SPTBN4 was set to GREEN Added comment: Biallelic pathogenic SPTBN4 variants cause Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (MIM #617519). There are several reports on the phenotype of relevant affected individuals with severe/profound DD/ID in at least 9 individuals : - Knierim et al (2017 - PMID: 28540413) [1 affected individual] - Anazi et al (2017 - PMID: 28940097) [1] - Wang et al (2018 - PMID: 29861105) [6] - Pehlivan et al (2019 - PMID: 31230720) [1] A recent article by Häusler et al (2019 - PMID: 31857255) describes the phenotype of 2 sibs, both presenting with motor and speech delay, although the older one had reportedly 'normal' cognitive performance allowing attendance of regular school at the age of 6 years. Features include congenital hypotonia, severe DD and ID (in most as outlined above, ID was the primary indication for testing on several occasions), poor or absent reflexes and weakness secondary to axonal motor neuropathy, feeding and respiratory difficulties, hearing and visual impairment. Seizures have been reported in at least 4 unrelated individuals (3 by Wang et al / 1 by Pehlivan et al). Variants in most cases were nonsense/frameshift although biallelic missense variants have also been reported. Sibs in the report by Häusler et al harbored a homozygous splicing variant. SPTBN4 encodes a member of the beta-spectrin protein family that is expressed in the brain, peripheral nervous system, pancreas, and skeletal muscle. βIV spectrin links ankyrinG and clustered ion channels (at axon initial segments and nodes of Ranvier) to the axonal cytoskeleton. Pathogenic variants are proposed to disrupt the cytoskeletal machinery controlling proper localization of ion channels and function of axonal domains where ion channels are normally clustered in high density. Among the evidence provided : nerve biopsies from an affected individual displayed reduced nodal Na+ channels and no nodal KCNQ2 K+ channels / Loss of AnkyrinG and βIV spectrin in animal model resulted in loss of KCNQ2- and KCNQ3- subunit containing K+ channels. Apart from the ID / epilepsy panels please consider inclusion in other relevant ones. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | TNRC6B | Konstantinos Varvagiannis reviewed gene: TNRC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | CDC42BPB |
Konstantinos Varvagiannis gene: CDC42BPB was added gene: CDC42BPB was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CDC42BPB were set to 32031333 Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality Penetrance for gene: CDC42BPB were set to unknown Review for gene: CDC42BPB was set to GREEN Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing. Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering. Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25). As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2). Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression. The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66). CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes). Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog). Please consider inclusion with amber / green rating in the ID panel (>=4 relevant individuals / variants) and other panels (e.g. for epilepsy, ASD). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | ADAM22 | Rebecca Foulger Classified gene: ADAM22 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | ADAM22 | Rebecca Foulger Added comment: Comment on list classification: Set rating as Amber: 2 unrelated families with ID as part of the phenotype (PMID:27066583 and 30237576). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | ADAM22 | Rebecca Foulger Gene: adam22 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.34 | ADAM22 | Rebecca Foulger commented on gene: ADAM22: PMID:27066583. Muona et al., 2016 report a Finnish proband-parent-trio with intractable seizures and ID. Compound het variants c.1202G>A, p.Cys401Tyr and c.2396delG, p.Ser799IlefsTer96 were found in ADAM22. Functional assays showed that mutant proteins failed to form the LGI1-ADAM22 ligand-receptor complex. The variants are unlikely to be full LOF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.34 | ADAM22 | Rebecca Foulger commented on gene: ADAM22: PMID:30237576 (Maddirevula et al., 2019) searched their database of clinical exomes for homozygous variants and report an 18 year old male with Arg860* variant and recurrent seizures (Supplementary Table). His development was normal until 5 months when he had a slower gain of milestones. He has ID with severely delayed speech. Family history revealed ID and epilepsy in his old brother and in wider family. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.34 | ADAM22 |
Rebecca Foulger gene: ADAM22 was added gene: ADAM22 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAM22 were set to 27066583; 30237576 Added comment: Added ADAM22 to ID panel based on literature curation for Epilepsy phenotype. Patients in PMID:27066583 (Finnish trio with compound het ADAM22 variants in the proband) and PMID:30237576 (18 year old male with Arg860* variant) both report ID alongside epilepsy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.33 | VPS51 |
Zornitza Stark gene: VPS51 was added gene: VPS51 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS51 were set to 30624672; 31207318 Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606 Review for gene: VPS51 was set to AMBER Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.33 | LRRC32 |
Zornitza Stark gene: LRRC32 was added gene: LRRC32 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC32 were set to 30976112 Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy Review for gene: LRRC32 was set to AMBER Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.33 | CTU2 | Rebecca Foulger Classified gene: CTU2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.33 | CTU2 | Rebecca Foulger Added comment: Comment on list classification: Gene was added to panel and rated Green by Zornitza Stark. Sufficient cases of global DD in PMID:31301155 in patients that survived infancy to support causation. Therefore updated rating from Grey to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.33 | CTU2 | Rebecca Foulger Gene: ctu2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.32 | CTU2 | Rebecca Foulger commented on gene: CTU2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.32 | CTU2 | Rebecca Foulger Phenotypes for gene: CTU2 were changed from Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142 to DREAM‐PL syndrome; Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, 618142 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | CDK19 | Zornitza Stark reviewed gene: CDK19: Rating: GREEN; Mode of pathogenicity: None; Publications: 32330417; Phenotypes: Intellectual disability, epileptic encephalopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | GNAI2 |
Zornitza Stark gene: GNAI2 was added gene: GNAI2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNAI2 were set to 31036916; 27787898 Phenotypes for gene: GNAI2 were set to Syndromic intellectual disability Review for gene: GNAI2 was set to AMBER Added comment: Two individuals reported, some functional data. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | FEM1B |
Zornitza Stark gene: FEM1B was added gene: FEM1B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FEM1B were set to 31036916 Phenotypes for gene: FEM1B were set to Syndromic intellectual disability Review for gene: FEM1B was set to AMBER Added comment: PMID: 31036916 - a single individual with de novo variant reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. The variant is in a highly constrained region of the protein. Cannot be certain the DDD and GeneMatcher individuals are unrelated, therefore I have treated as two reports for now. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | WIPI2 |
Zornitza Stark gene: WIPI2 was added gene: WIPI2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: WIPI2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WIPI2 were set to 30968111 Phenotypes for gene: WIPI2 were set to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 Review for gene: WIPI2 was set to RED Added comment: Four homozygous individuals from one consanguineous family with intellectual disability, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function. One to watch. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | GSX2 |
Zornitza Stark gene: GSX2 was added gene: GSX2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GSX2 were set to 31412107 Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646; Intellectual disability; Dystonia; Spastic tetra paresis Review for gene: GSX2 was set to AMBER Added comment: Two unrelated families, some functional data. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | YARS |
Zornitza Stark gene: YARS was added gene: YARS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: YARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YARS were set to 30304524; 29232904; 27633801 Phenotypes for gene: YARS were set to Intellectual disability; deafness; nystagmus; liver dysfunction Review for gene: YARS was set to GREEN gene: YARS was marked as current diagnostic Added comment: Mono-allelic variants are associated with CMT. However, 10 individuals from three unrelated families reported with bi-allelic variants and a severe phenotype, comprising ID, nystagmus, deafness, liver dysfunction and a range of other features. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | CACNB4 | Zornitza Stark reviewed gene: CACNB4: Rating: AMBER; Mode of pathogenicity: None; Publications: 32176688; Phenotypes: Intellectual disability, epilepsy, movement disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | CEP55 | Rebecca Foulger Classified gene: CEP55 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | CEP55 | Rebecca Foulger Added comment: Comment on list classification: Rated CEP55 as Green: >3 unrelated cases in PMID:32100459 with DD/ID (2 of which are severe). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.31 | CEP55 | Rebecca Foulger Gene: cep55 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.30 | CEP55 | Rebecca Foulger changed review comment from: PMID:32100459 (Barrie et al., 2020) describe 7 living individuals (5 families) with biallelic variants (compound het and homozygous splice site variant) in CEP55. Global/severe DD was seen in patient 2, and the 3 siblings (patients 5,6,7). Mild/delayed motor/speech development was seen in unrelated patients 3 and 4.; to: PMID:32100459 (Barrie et al., 2020) describe 7 living individuals (5 families) with biallelic variants (compound het and homozygous splice site variant) in CEP55. Global/severe DD was seen in patient 2, and the 3 siblings (patients 5,6,7). Mild/delayed motor & speech development was seen in unrelated patients 3 and 4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.30 | CEP55 | Rebecca Foulger changed review comment from: PMID:32100459 (Barrie et al., 2020) describe 7 living individuals (5 families) with biallelic variants (compound het and homozygous splice site variant) in CEP55. Global/severe DD wax seen in patient 2, and the 3 siblings (patients 5,6,7). Mild/delayed motor/speech development was seen in unrelated patients 3 and 4.; to: PMID:32100459 (Barrie et al., 2020) describe 7 living individuals (5 families) with biallelic variants (compound het and homozygous splice site variant) in CEP55. Global/severe DD was seen in patient 2, and the 3 siblings (patients 5,6,7). Mild/delayed motor/speech development was seen in unrelated patients 3 and 4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.30 | CEP55 | Rebecca Foulger commented on gene: CEP55: PMID:32100459 (Barrie et al., 2020) describe 7 living individuals (5 families) with biallelic variants (compound het and homozygous splice site variant) in CEP55. Global/severe DD wax seen in patient 2, and the 3 siblings (patients 5,6,7). Mild/delayed motor/speech development was seen in unrelated patients 3 and 4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.30 | CEP55 |
Rebecca Foulger gene: CEP55 was added gene: CEP55 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP55 were set to 32100459 Phenotypes for gene: CEP55 were set to microcephaly, delayed development, and bilateral toe syndactyly Added comment: Added to ID panel on advice from Helen Brittain, Genomics England Clinical Team. Phenotype of living individuals in PMID:32100459 (Barrie et al., 2020) includes developmental delay. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.29 | RSRC1 | Zornitza Stark edited their review of gene: RSRC1: Added comment: 17 additional individuals reported.; Changed rating: GREEN; Changed publications: 28640246, 29522154, 32227164; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 70, MIM# 618402; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.29 | EIF2AK2 |
Zornitza Stark gene: EIF2AK2 was added gene: EIF2AK2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK2 were set to 32197074 Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness Review for gene: EIF2AK2 was set to GREEN gene: EIF2AK2 was marked as current diagnostic Added comment: Eight individuals with de novo variants and complex neurodevelopmental phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.29 | EIF2AK1 |
Zornitza Stark gene: EIF2AK1 was added gene: EIF2AK1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: EIF2AK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK1 were set to 32197074 Phenotypes for gene: EIF2AK1 were set to Intellectual disability; white matter abnormalities Review for gene: EIF2AK1 was set to RED Added comment: Single individual reported with de novo variant in this gene, one to watch. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.29 | NRROS |
Zornitza Stark gene: NRROS was added gene: NRROS was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRROS were set to 32100099; 32197075 Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy Review for gene: NRROS was set to GREEN Added comment: Normal development or mild developmental delay until onset of regression around age of 1 concurrent with epilepsy Biallelic LOF mutations with functional evidence of pathogenicity reported in 6 unrelated families. Suggest also add to Epilepsy panel, possibly others. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.29 | NOVA2 |
Zornitza Stark gene: NOVA2 was added gene: NOVA2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOVA2 were set to 32197073 Phenotypes for gene: NOVA2 were set to Intellectual disability; autism; hypotonia; spasticity; ataxia Review for gene: NOVA2 was set to GREEN gene: NOVA2 was marked as current diagnostic Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.29 | GAD1 | Sarah Leigh Phenotypes for gene: GAD1 were changed from ?Cerebral palsy, spastic quadriplegic, 1; Developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele to ?Cerebral palsy, spastic quadriplegic, 1 603513; Developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.28 | GAD1 | Sarah Leigh Publications for gene: GAD1 were set to 26503795; 24896178; 26350204; https://doi-org.ezproxy.library.qmul.ac.uk/10.1093/brain/awaa085 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.27 | GAD1 | Sarah Leigh Added comment: Comment on publications: https://doi-org.ezproxy.library.qmul.ac.uk/10.1093/brain/awaa085 new publication, without a PMID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.27 | GAD1 | Sarah Leigh Publications for gene: GAD1 were set to 26503795; 24896178; 26350204; https://doi-org.ezproxy.library.qmul.ac.uk/10.1093/brain/awaa085 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.27 | GAD1 | Sarah Leigh Added comment: Comment on publications: https://doi-org.ezproxy.library.qmul.ac.uk/10.1093/brain/awaa085 new publication, without a PMID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.27 | GAD1 | Sarah Leigh Publications for gene: GAD1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.26 | GAD1 | Sarah Leigh Phenotypes for gene: GAD1 were changed from ?Cerebral palsy, spastic quadriplegic, 1 to ?Cerebral palsy, spastic quadriplegic, 1; Developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.25 | GAD1 | Sarah Leigh Classified gene: GAD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.25 | GAD1 | Sarah Leigh Added comment: Comment on list classification: Five biallelic loss of function variants reported in 11 cases in 6 unrelated families. All cases had epilepsy syndrome, 10 profound intellectual disabilty (1 case died at day 9 of life) and other nuerological and developement features. Supportive functional studies were also presented | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.25 | GAD1 | Sarah Leigh Gene: gad1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | NUP188 | Zornitza Stark reviewed gene: NUP188: Rating: GREEN; Mode of pathogenicity: None; Publications: 32021605, 28726809, 32275884; Phenotypes: microcephaly, ID, cataract, structural brain abnormalities, hypoventilation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | PIGK |
Zornitza Stark changed review comment from: 12 individuals from 9 unrelated families reported. Sources: Expert list; to: 12 individuals from 9 unrelated families reported. Suggest adding to Genetic Epilepsy panel as well. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | PIGK |
Zornitza Stark gene: PIGK was added gene: PIGK was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGK were set to 32220290 Phenotypes for gene: PIGK were set to Intellectual disability; seizures; cerebellar atrophy Review for gene: PIGK was set to GREEN gene: PIGK was marked as current diagnostic Added comment: 12 individuals from 9 unrelated families reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | ADARB1 |
Zornitza Stark changed review comment from: Four unrelated individuals with bi-allelic variants in this gene. Sources: Literature; to: Four unrelated individuals with bi-allelic variants in this gene. Suggest also adding to Genetic Epilepsy and Microcephaly panels. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | ADARB1 |
Zornitza Stark gene: ADARB1 was added gene: ADARB1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADARB1 were set to 32220291 Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures Review for gene: ADARB1 was set to GREEN gene: ADARB1 was marked as current diagnostic Added comment: Four unrelated individuals with bi-allelic variants in this gene. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | RNF13 | Sarah Leigh Classified gene: RNF13 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.24 | RNF13 | Sarah Leigh Gene: rnf13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.23 | RNF13 |
Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive functional studies.; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive functional studies. Gain-of-function mechanism has been reported, therefore the mutational spectrum may be limited and is still to be determined through further cases or further functional studies (view of Helen Britain, GeL Clincial Fellow). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.23 | SCAMP5 | Sarah Leigh Tag watchlist tag was added to gene: SCAMP5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.23 | SCAMP5 |
Sarah Leigh changed review comment from: Comment on list classification: Not associated with phenotype in OMIM (last edited on 10/06/2014) or in Gen2Phen. Two variants have been identified in three unrelated cases (one monoallelic, one biallelic). Supportive functional studies have been reported. It would appear that the two variants reported so far in this gene result in differing mode of pathogenicity and phenotypic features. With heterozygous c.538G>T, p.Gly180Trp seeming to have a dominant-negative effect resulting in autistic spectrum disorder, intellectual disability and seizures. While homozygous c.271C>T, p.R91W seems to have a loss of function effect resulting in early onset epilepsy and Parkinson’s disease. This may be due to different functional domains of the mature protein being altered.; to: Comment on list classification: Not associated with phenotype in OMIM (last edited on 10/06/2014) or in Gen2Phen. Two variants have been identified in three unrelated cases (one monoallelic, one biallelic). Supportive functional studies have been reported. It would appear that the two variants reported so far in this gene result in differing mode of pathogenicity and phenotypic features. With heterozygous c.538G>T, p.Gly180Trp seeming to have a dominant-negative effect resulting in autistic spectrum disorder, intellectual disability and seizures. While homozygous c.271C>T, p.R91W seems to have a loss of function effect resulting in early onset epilepsy and Parkinson’s disease. This may be due to different functional domains of the mature protein being altered. Based on this evidence, SCAMP5 is rated as Amber, with a Watchlist tag. This status may change if further cases are reported. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.23 | SCN8A | Sarah Leigh Added comment: Comment on mode of pathogenicity: Based on report in PMID 31625145, reporting biallelic loss of function SCN8A variants in three cases in two families with severe developmental and epileptic encephalopathy. This differs from the previosly reported gain of function monoallelic variants (PMID 24194747;22365152). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.23 | SCN8A | Sarah Leigh Mode of pathogenicity for gene: SCN8A was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.22 | SCN8A | Sarah Leigh Added comment: Comment on mode of inheritance: Based on report in PMID 31625145, reporting biallelic loss of function SCN8A variants in three cases in two families with severe developmental and epileptic encephalopathy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.22 | SCN8A | Sarah Leigh Mode of inheritance for gene: SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.21 | SCN8A | Sarah Leigh Phenotypes for gene: SCN8A were changed from Cognitive impairment with or without cerebellar ataxia, 614306Epileptic encephalopathy, early infantile, 13, 614558; COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA to ?Cognitive impairment with or without cerebellar ataxia,614306; Epileptic encephalopathy, early infantile,614558; Seizures, benign familial infantile,617080 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.20 | SCN8A | Sarah Leigh Publications for gene: SCN8A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.19 | SCAMP5 | Sarah Leigh Added comment: Comment on mode of pathogenicity: Heterozygous c.538G>T, p.Gly180Trp seeming to have a dominant-negative effect resulting in autistic spectrum disorder, intellectual disability and seizures. While homozygous c.271C>T, p.R91W seems to have a loss of function effect resulting in early onset epilepsy and Parkinson’s disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.19 | SCAMP5 | Sarah Leigh Mode of pathogenicity for gene: SCAMP5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.18 | SCAMP5 | Sarah Leigh Classified gene: SCAMP5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.18 | SCAMP5 |
Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM (last edited on 10/06/2014) or in Gen2Phen. Two variants have been identified in three unrelated cases (one monoallelic, one biallelic). Supportive functional studies have been reported. It would appear that the two variants reported so far in this gene result in differing mode of pathogenicity and phenotypic features. With heterozygous c.538G>T, p.Gly180Trp seeming to have a dominant-negative effect resulting in autistic spectrum disorder, intellectual disability and seizures. While homozygous c.271C>T, p.R91W seems to have a loss of function effect resulting in early onset epilepsy and Parkinson’s disease. This may be due to different functional domains of the mature protein being altered. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.18 | SCAMP5 | Sarah Leigh Gene: scamp5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.17 | SCAMP5 | Sarah Leigh Added comment: Comment on mode of inheritance: Based on the reporting of a de novo heterozygous varaiant (NM_001178111.1:c.538G>T) in two unrelated cases (PMID: 31439720) and a homozygous variant (NM_001178111:c.271C>T, rs747966691) in two members of a Chinese consanguienious family (PMID: 32020363). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.17 | SCAMP5 | Sarah Leigh Mode of inheritance for gene: SCAMP5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.16 | SCAMP5 | Sarah Leigh Publications for gene: SCAMP5 were set to 31439720; 20071347 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.15 | RNF13 | Sarah Leigh reviewed gene: RNF13: 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: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.15 | RNF113A | Sarah Leigh Classified gene: RNF113A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.15 | RNF113A | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene for X-linked trichothiodystrophy. At least 3 terminating variants reported in unrelated cases. Supportive functional studies also reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.15 | RNF113A | Sarah Leigh Gene: rnf113a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.14 | RNF113A | Sarah Leigh Publications for gene: RNF113A were set to 25612912; 29144457 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.13 | RARS | Sarah Leigh Classified gene: RARS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.13 | RARS | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 19 variants reported in at least 13 cases of Hypomyelinating Leukodystrophy exhibinting intellectual disability to varying degrees. Supportive functional studies were also reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.13 | RARS | Sarah Leigh Gene: rars has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.12 | RARS | Sarah Leigh commented on gene: RARS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.12 | RARS | Sarah Leigh Tag new-gene-name tag was added to gene: RARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.12 | RALGAPA1 | Sarah Leigh Classified gene: RALGAPA1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.12 | RALGAPA1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for RALGAPA1-related neurodevelopmental disorder. At least 5 variants reported in at least 4 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.12 | RALGAPA1 | Sarah Leigh Gene: ralgapa1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.11 | RALGAPA1 | Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;hypotonia;infantile spasms. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.11 | RALGAPA1 | Sarah Leigh Phenotypes for gene: RALGAPA1 were changed from Intellectual disability; hypotonia; infantile spasms. to Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation 618797 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.10 | PUM1 | Sarah Leigh Classified gene: PUM1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.10 | PUM1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 SNVs in at least 5 unrelated cases and CNVs spanning PUM1 in 9 cases. Supportive functional studies also reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.10 | PUM1 | Sarah Leigh Gene: pum1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.9 | PUM1 | Sarah Leigh Added comment: Comment on phenotypes: Global developmental delay;Intellectual disability;Seizures;Abnormality of the face;Ataxia;Cryptorchidism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.9 | PUM1 | Sarah Leigh Phenotypes for gene: PUM1 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of the face; Ataxia; Cryptorchidism to Spinocerebellar ataxia 47 617931 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.8 | PUM1 | Sarah Leigh Publications for gene: PUM1 were set to 29474920; 30903679; 31859446 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.7 | PIGP | Sarah Leigh Classified gene: PIGP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.7 | PIGP |
Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported (rs768633670, rs778481061). rs768633670 were reported as a compound heterozygotes in one case and was present in at least two geographically separated consanguineous European families; suggesting a founder effect in the European population (PMID 32042915). Supportive functional studies are also presented. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.7 | PIGP | Sarah Leigh Gene: pigp has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.6 | PIGP | Sarah Leigh Publications for gene: PIGP were set to 28334793; 31139695; 32042915 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.5 | PIGP | Sarah Leigh Phenotypes for gene: PIGP were changed from ?Epileptic encephalopathy, early infantile, 55, 617599; Generalized hypotonia; Global developmental delay; Seizures; Intellectual disability; Feeding difficulties; Cortical visual impairment to Epileptic encephalopathy, early infantile, 55, 617599; Generalized hypotonia; Global developmental delay; Seizures; Intellectual disability; Feeding difficulties; Cortical visual impairment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.4 | PIGP | Sarah Leigh Publications for gene: PIGP were set to 28334793; 31139695; 32042915 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.4 | PIGP | Sarah Leigh Publications for gene: PIGP were set to 28334793; 31139695 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | SLC5A6 | Zornitza Stark reviewed gene: SLC5A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31754459, 27904971, 31392107; Phenotypes: Developmental delay, epilepsy, neurodegeneration; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RARS | Zornitza Stark reviewed gene: RARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31814314; Phenotypes: Leukodystrophy, hypomyelinating, 9 (# 616140); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | CXorf56 | Zornitza Stark reviewed gene: CXorf56: Rating: GREEN; Mode of pathogenicity: None; Publications: 29374277, 31822863; Phenotypes: Mental retardation, X-linked 107, MIM# 301013; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | TNR |
Zornitza Stark gene: TNR was added gene: TNR was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: TNR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNR were set to 32099069 Phenotypes for gene: TNR were set to Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus Review for gene: TNR was set to GREEN gene: TNR was marked as current diagnostic Added comment: 13 individuals from 8 unrelated families reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RUSC2 |
Zornitza Stark gene: RUSC2 was added gene: RUSC2 was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: RUSC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RUSC2 were set to 27612186 Phenotypes for gene: RUSC2 were set to Mental retardation, autosomal recessive 61, MIM# 617773 Review for gene: RUSC2 was set to AMBER Added comment: Two unrelated families reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RUNX2 | Zornitza Stark reviewed gene: RUNX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleidocranial dysplasia, MIM# 119600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RSRC1 |
Zornitza Stark gene: RSRC1 was added gene: RSRC1 was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: RSRC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RSRC1 were set to 28640246; 29522154 Phenotypes for gene: RSRC1 were set to Intellectual developmental disorder, autosomal recessive 70, MIM# 618402 Review for gene: RSRC1 was set to AMBER Added comment: Two unrelated families reported, 8 affected individuals. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RSPO4 | Zornitza Stark reviewed gene: RSPO4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Anonychia congenita, MIM# 206800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RSPH3 | Zornitza Stark reviewed gene: RSPH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 32, MIM# 616481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RSPH1 | Zornitza Stark reviewed gene: RSPH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 24, MIM# 615481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RPS19 | Zornitza Stark reviewed gene: RPS19: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Diamond-Blackfan anemia 1, MIM#105650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RPGRIP1 | Zornitza Stark reviewed gene: RPGRIP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 13, MIM# 608194, Leber congenital amaurosis 6, MIM# 613826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RPE65 | Zornitza Stark reviewed gene: RPE65: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 2, MIM# 204100, Retinitis pigmentosa 20, MIM# 613794, Retinitis pigmentosa 87 with choroidal involvement, MIM# 618697; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | ROBO3 | Zornitza Stark reviewed gene: ROBO3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1 607313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RNF13 | Zornitza Stark reviewed gene: RNF13: Rating: GREEN; Mode of pathogenicity: None; Publications: 30595371; Phenotypes: Epileptic encephalopathy, early infantile, 73, MIM# 618379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RIC1 |
Zornitza Stark gene: RIC1 was added gene: RIC1 was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RIC1 were set to 31932796 Phenotypes for gene: RIC1 were set to Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD Review for gene: RIC1 was set to AMBER Added comment: Zebrafish model and consanguineous families but homozygous-by-descent. One to watch. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RHEB | Zornitza Stark reviewed gene: RHEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29051493; Phenotypes: Intellectual disability, Macrocephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | RETREG1 | Zornitza Stark reviewed gene: RETREG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MYO5B | Zornitza Stark reviewed gene: MYO5B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microvillus inclusion disease, MIM# 251850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MYH9 | Zornitza Stark reviewed gene: MYH9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MYH8 | Zornitza Stark reviewed gene: MYH8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Trismus-pseudocamptodactyly syndrome, MIM# 158300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MYH6 | Zornitza Stark reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Sick sinus syndrome 3} 614090 3 Atrial septal defect 3, MIM# 614089, Cardiomyopathy, dilated, 1EE, MIM# 613252, Cardiomyopathy, hypertrophic, 14, MIM# 613251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MTHFS | Zornitza Stark reviewed gene: MTHFS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30031689, 31844630, 22303332; Phenotypes: Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MSX2 | Zornitza Stark reviewed gene: MSX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis 2, MIM# 604757, Parietal foramina 1, MIM# 168500, Parietal foramina with cleidocranial dysplasia, MIM# 168550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MSX1 | Zornitza Stark reviewed gene: MSX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia 3, Witkop type 189500, Orofacial cleft 5 608874, Tooth agenesis, selective, 1, with or without orofacial cleft 106600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MPV17 | Zornitza Stark reviewed gene: MPV17: Rating: GREEN; Mode of pathogenicity: None; Publications: 22593919; Phenotypes: Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM #256810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MNX1 | Zornitza Stark reviewed gene: MNX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Currarino syndrome, OMIM #176450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MN1 | Zornitza Stark reviewed gene: MN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31834374, 31839203; Phenotypes: Intellectual disability, dysmophic features, rhombencephalosynapsis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MMP13 | Zornitza Stark reviewed gene: MMP13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 1, MIM# 602111, Metaphyseal dysplasia, Spahr type, MIM# 250400, Spondyloepimetaphyseal dysplasia, Missouri type, MIM# 602111; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MGP | Zornitza Stark reviewed gene: MGP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Keutel syndrome, MIM# 245150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | MFSD2A | Zornitza Stark reviewed gene: MFSD2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005865, 26005868, 24828044; Phenotypes: Microcephaly 15, primary, autosomal recessive, MIM# 616486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||