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Severe microcephaly v2.40 METTL5 Arina Puzriakova Classified gene: METTL5 as Amber List (moderate evidence)
Severe microcephaly v2.40 METTL5 Arina Puzriakova Added comment: Comment on list classification: Borderline Green/Amber gene. Sufficient unrelated cases (3) from literature and supportive animal models, but uncertain functional significance of one variant. Thus METTL5 will be flagged for review of evidence at the next GMS panel update (added 'for-review' tag)
Severe microcephaly v2.40 METTL5 Arina Puzriakova Gene: mettl5 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.39 METTL5 Arina Puzriakova gene: METTL5 was added
gene: METTL5 was added to Severe microcephaly. Sources: Literature
for-review tags were added to gene: METTL5.
Mode of inheritance for gene: METTL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: METTL5 were set to 29302074; 31564433; https://imgc2019.sciencesconf.org/data/abstract_book_complete.pdf
Phenotypes for gene: METTL5 were set to Intellectual developmental disorder, autosomal recessive 72, 618665
Added comment: Associated with 'Intellectual developmental disorder' in OMIM, and is a 'probable' gene for 'Autosomal-Recessive Intellectual Disability and Microcephaly' in DD-G2P.

Gene added and expert reviewed on Intellectual Disability panel: https://panelapp.genomicsengland.co.uk/panels/285/gene/METTL5/

Distinct biallelic variants reported in 3 unrelated families (total 9 individuals) with severe microcephaly (OFC -2.8 to -8 SD) and intellectual disability. Mouse and zebrafish models appeared to recapitulate relevant human phenotypes (microcephaly, ID and growth retardation).

However, the Gly61Asp variant found in the PMID:29302074 siblings is currently classified VUS as localisation and expression studies failed to demonstrate a functional impact on the encoded protein.
Sources: Literature
Severe microcephaly v2.38 MFSD2A Arina Puzriakova Phenotypes for gene: MFSD2A were changed from Microcephaly 15, primary, autosomal recessive, 616486 to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities, 616486
Severe microcephaly v2.37 MFSD2A Arina Puzriakova Added comment: Comment on publications: Added publications to support this gene-disease association
Severe microcephaly v2.37 MFSD2A Arina Puzriakova Publications for gene: MFSD2A were set to 12046007
Severe microcephaly v2.36 ZNF335 Arina Puzriakova Publications for gene: ZNF335 were set to 25951892; 25548773; 23178126
Severe microcephaly v2.35 ZNF335 Arina Puzriakova Phenotypes for gene: ZNF335 were changed from Autosomal recessive primary microcephaly (MCPH) ; ?Microcephaly 10, primary, autosomal recessive, 615095 to Microcephaly 10, primary, autosomal recessive, 615095
Severe microcephaly v2.34 ZNF335 Arina Puzriakova Classified gene: ZNF335 as Amber List (moderate evidence)
Severe microcephaly v2.34 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).
Severe microcephaly v2.34 ZNF335 Arina Puzriakova Gene: znf335 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.33 ZNF335 Arina Puzriakova Tag for-review tag was added to gene: ZNF335.
Severe microcephaly v2.33 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
Severe microcephaly v2.33 TTC5 Sarah Leigh Deleted their comment
Severe microcephaly v2.33 CEP55 Arina Puzriakova Classified gene: CEP55 as Amber List (moderate evidence)
Severe microcephaly v2.33 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).
Severe microcephaly v2.33 CEP55 Arina Puzriakova Gene: cep55 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.32 CEP55 Arina Puzriakova Tag for-review tag was added to gene: CEP55.
Severe microcephaly v2.32 TMX2 Arina Puzriakova Classified gene: TMX2 as Amber List (moderate evidence)
Severe microcephaly v2.32 TMX2 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).
Severe microcephaly v2.32 TMX2 Arina Puzriakova Gene: tmx2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.31 TMX2 Arina Puzriakova Tag for-review tag was added to gene: TMX2.
Severe microcephaly v2.31 UBE3A Sarah Leigh Phenotypes for gene: UBE3A were changed from Angelman syndrome MIM#105830 to Angelman syndrome 105830
Severe microcephaly v2.30 UBE3A Sarah Leigh Publications for gene: UBE3A were set to
Severe microcephaly v2.29 UBE3A Sarah Leigh Classified gene: UBE3A as Amber List (moderate evidence)
Severe microcephaly v2.29 UBE3A Sarah Leigh Gene: ube3a has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.28 UBE3A Sarah Leigh Tag for-review tag was added to gene: UBE3A.
Severe microcephaly v2.28 UBE3A Sarah Leigh edited their review of gene: UBE3A: Added comment: Postnatal microcephaly has been reported in Angelman syndrome patients, mostly amonst those with deletions rather than UPD of 15q.; Changed rating: AMBER; Changed publications: 2012134, 9182785, 10861661, 10861661; Changed phenotypes: Angelman syndrome 105830; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Severe microcephaly v2.28 UBE3A Sarah Leigh Added comment: Comment on mode of inheritance: In accordance with http://igc.otago.ac.nz/home.html
Severe microcephaly v2.28 UBE3A Sarah Leigh Mode of inheritance for gene: UBE3A was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Severe microcephaly v2.27 LMNB2 Konstantinos Varvagiannis gene: LMNB2 was added
gene: LMNB2 was added to Severe microcephaly. 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
Severe microcephaly v2.27 LMNB1 Konstantinos Varvagiannis gene: LMNB1 was added
gene: LMNB1 was added to Severe microcephaly. 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 33033404
Phenotypes for gene: LMNB1 were set to Congenital microcephaly; Global developmental delay; Intellectual disability
Penetrance for gene: LMNB1 were set to Complete
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: 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
Severe microcephaly v2.27 DNMT3A Rachel Jones reviewed gene: DNMT3A: 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: PID: 30478443; Phenotypes: 618724 HEYN-SPROUL-JACKSON SYNDROME, HESJAS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v2.27 YIF1B Arina Puzriakova Tag for-review was removed from gene: YIF1B.
Tag watchlist tag was added to gene: YIF1B.
Severe microcephaly v2.27 YIF1B Arina Puzriakova Tag for-review tag was added to gene: YIF1B.
Severe microcephaly v2.27 YIF1B Arina Puzriakova Classified gene: YIF1B as Amber List (moderate evidence)
Severe microcephaly v2.27 YIF1B Arina Puzriakova Added comment: Comment on list classification: Although 5/6 individuals described in PMID:32006098 had microcephaly, 4 of these share the same founder variant and the severity of microcephaly is not specified. Therefore, rating Amber until further cases are reported (added to watchlist).
Severe microcephaly v2.27 YIF1B Arina Puzriakova Gene: yif1b has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.26 NUP188 Arina Puzriakova Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804
Severe microcephaly v2.25 NUP188 Arina Puzriakova Classified gene: NUP188 as Amber List (moderate evidence)
Severe microcephaly v2.25 NUP188 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next major review - progressive microcephaly reported in at least 5 affected individuals due to biallelic truncating variants in NUP188.
Severe microcephaly v2.25 NUP188 Arina Puzriakova Gene: nup188 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.24 NUP188 Arina Puzriakova Tag for-review tag was added to gene: NUP188.
Severe microcephaly v2.24 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
Severe microcephaly v2.24 RAD50 Arina Puzriakova Tag watchlist tag was added to gene: RAD50.
Severe microcephaly v2.24 RAD50 Arina Puzriakova Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder, MIM# 613078 to Nijmegen breakage syndrome-like disorder, 613078
Severe microcephaly v2.23 RAD50 Arina Puzriakova Publications for gene: RAD50 were set to 19409520; 32212377
Severe microcephaly v2.22 RAD50 Arina Puzriakova Classified gene: RAD50 as Amber List (moderate evidence)
Severe microcephaly v2.22 RAD50 Arina Puzriakova Added comment: Comment on list classification: Relevant phenotype (two unrelated cases with severe congenital microcephaly) but additional cases required before inclusion of RAD50 on a diagnostic panel.

Rating Amber in anticipation of additional publications/clinical evidence (added to watchlist).
Severe microcephaly v2.22 RAD50 Arina Puzriakova Gene: rad50 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.21 RAD50 Zornitza Stark gene: RAD50 was added
gene: RAD50 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD50 were set to 19409520; 32212377
Phenotypes for gene: RAD50 were set to Nijmegen breakage syndrome-like disorder, MIM# 613078
Review for gene: RAD50 was set to GREEN
gene: RAD50 was marked as current diagnostic
Added comment: Two individuals reported with bi-allelic variants in this gene showing dysmorphic facial features similar to NBS, short stature, microcephaly, and mild/moderate intellectual disability. Fibroblasts established from one of the individuals showed chromosomal instability and abnormal radioresistant DNA synthesis. The MRE11/RAD50/NBN (MRN) complex is involved in signaling processes inducing the repair of DNA double-strand breaks. Variants in NBN and MRE11 are associated with Nijmegen breakage syndrome (NBS) and ataxia telangiectasia (AT)‐like disorder, respectively, so this gene is a strong biological candidate for this phenotype.
Sources: Literature
Severe microcephaly v2.21 EXOC7 Arina Puzriakova Classified gene: EXOC7 as Amber List (moderate evidence)
Severe microcephaly v2.21 EXOC7 Arina Puzriakova Added comment: Comment on list classification: Though mild microcephaly reported in 5/8 cases (-0.5 to -2.6 SD), rating Amber as severity of presentation is not within the scope of this panel.
Severe microcephaly v2.21 EXOC7 Arina Puzriakova Gene: exoc7 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.20 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
gene: YIF1B was marked as current diagnostic
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID 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. 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 KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). 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.
Sources: Expert list
Severe microcephaly v2.20 UNC80 Zornitza Stark gene: UNC80 was added
gene: UNC80 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: UNC80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC80 were set to 26708751; 26708753; 26545877; 29572195
Phenotypes for gene: UNC80 were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 MIM#616801
Review for gene: UNC80 was set to GREEN
gene: UNC80 was marked as current diagnostic
Added comment: Summary: Many patients reported as microcephalic. Not all have head circumference < -3SD but there are at least 3 unrelated individuals reported with head circumference smaller than this.

PMID 26708751: 4 individuals from 3 families reported. At 4 years one had OFC -4SD (the others 2nd centile at 4yo, 3rd centile at 15yo, and 10th centile at 9yo).

PMID 26708753: Two 'not directly related' families F1 and F2 identified with the same variant. A third and fourth family had different variants. All affected individuals described were microcephalic (F1: -3.2SD at 4yo; F2: -4SD at 2yo and -2.9SD at 13mo; F3: -2.4SD at 7yo; F4: 9th centile at 4yo and 5th centile at 8yo).

PMID 26545877: 7 affected individuals from 2 distantly related families with the same nonsense variant were all microcephalic (<2nd centile).

PMID 29572195: 2 unrelated individuals reported. Head circumference of patient 1 was -0.5SD at 9yo; Patient 2 -3.7SD at 3yo.
Sources: Expert list
Severe microcephaly v2.20 UGP2 Zornitza Stark gene: UGP2 was added
gene: UGP2 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGP2 were set to 31820119
Phenotypes for gene: UGP2 were set to Epileptic encephalopathy; intellectual disability; microcephaly
Review for gene: UGP2 was set to GREEN
gene: UGP2 was marked as current diagnostic
Added comment: 22 individuals from 15 families reported with the same homozygous missense variant in this gene, chr2:64083454A > G, which causes a disruption of the start codon in the shorter isoform, which is expressed in brain.
Sources: Expert list
Severe microcephaly v2.20 UBE3A Zornitza Stark gene: UBE3A was added
gene: UBE3A was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: UBE3A was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Phenotypes for gene: UBE3A were set to Angelman syndrome MIM#105830
Review for gene: UBE3A was set to GREEN
gene: UBE3A was marked as current diagnostic
Added comment: Microcephaly is a key feature.
Sources: Expert list
Severe microcephaly v2.20 TSEN54 Zornitza Stark gene: TSEN54 was added
gene: TSEN54 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN54 were set to 20952379; 20301773
Phenotypes for gene: TSEN54 were set to Pontocerebellar hypoplasia type 2A (MIM#277470) and type 4 (MIM#225753)
Review for gene: TSEN54 was set to GREEN
gene: TSEN54 was marked as current diagnostic
Added comment: Microcephaly is a common feature of TSEN54 pontocerebellar hypoplasia (progressive in type 2, present at birth in type 4).
Sources: Expert list
Severe microcephaly v2.20 TSEN15 Zornitza Stark gene: TSEN15 was added
gene: TSEN15 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to 27392077
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F MIM#617026
Review for gene: TSEN15 was set to GREEN
gene: TSEN15 was marked as current diagnostic
Added comment: PMID 27392077 Reports four individuals from three families with PCH type 2 and different homozygous missense variants, all had progressive microcephaly (between -3SD and -9.7SD). Functional studies indicated that all variants resulted in almost complete lack of in vitro tRNA cleavage activity.
Sources: Expert list
Severe microcephaly v2.20 TRIO Zornitza Stark gene: TRIO was added
gene: TRIO was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TRIO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIO were set to 26721934; 32109419
Phenotypes for gene: TRIO were set to Mental retardation, autosomal dominant 44, MIM# 617061
Review for gene: TRIO was set to GREEN
gene: TRIO was marked as current diagnostic
Added comment: The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1. Individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly.
Sources: Expert list
Severe microcephaly v2.20 DYNC1I2 Zornitza Stark gene: DYNC1I2 was added
gene: DYNC1I2 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492
Review for gene: DYNC1I2 was set to GREEN
gene: DYNC1I2 was marked as current diagnostic
Added comment: Five individuals from three unrelated families reported.
Sources: Expert list
Severe microcephaly v2.20 DPM1 Zornitza Stark gene: DPM1 was added
gene: DPM1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: DPM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPM1 were set to 16641202; 10642602; 10642597
Phenotypes for gene: DPM1 were set to Congenital disorder of glycosylation, type Ie 608799
Review for gene: DPM1 was set to GREEN
gene: DPM1 was marked as current diagnostic
Added comment: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.
Sources: Expert list
Severe microcephaly v2.20 DNMT3A Zornitza Stark gene: DNMT3A was added
gene: DNMT3A was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: DNMT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3A were set to 30478443
Phenotypes for gene: DNMT3A were set to intellectual disability; microcephaly; short stature
Review for gene: DNMT3A was set to GREEN
gene: DNMT3A was marked as current diagnostic
Added comment: Three individuals reported, two with the same de novo missense variant. Postulated to be GOF as opposed to LOF variants in this gene which cause an overgrowth syndrome. Animal model supports pathogenicity.
Sources: Expert list
Severe microcephaly v2.20 DNA2 Zornitza Stark reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24389050, 31045292; Phenotypes: Seckel syndrome 8, MIM#615807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Severe microcephaly v2.20 CTU2 Zornitza Stark gene: CTU2 was added
gene: CTU2 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 26633546
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (MIM#618142)
Review for gene: CTU2 was set to GREEN
gene: CTU2 was marked as current diagnostic
Added comment: Dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly and lissencephaly (DREAM-PL) as proposed by authors.

PMID: 26633546
- 3 consanguineous families all with the same splice variant (NM_001012762.1:c.873G>A). Assumed to be founder variant
- all had microcephaly but measurements were not provided

PMID: 27480277
- 2 additional patients from an extended consanguineous family with the same variant as above
- Patient 1: head circumference of -3.5SD at birth, not growing
- Patient 2: head circumference of -4.3 SD

PMID: 31301155
- 5 new patients with microcephaly (no measurements provided)
- 3x PTVs and 1x missense
Sources: Expert list
Severe microcephaly v2.20 CTSF Zornitza Stark gene: CTSF was added
gene: CTSF was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: CTSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTSF were set to 23746550; 30893510; 28619046
Phenotypes for gene: CTSF were set to Mental retardation, autosomal dominant 21 (MIM#615502)
Review for gene: CTSF was set to GREEN
gene: CTSF was marked as current diagnostic
Added comment: PMID: 23746550
- 4 probands, 2x PTV, 1x missense, 1x 280kb deletion (all de novo)
- OFCs ranges from -0.8 SD (the proband with the deletion) to -3.51 SD

PMID: 30893510
- 3 probands, de novo 2x PTV and 1x missense
- OFCs ranges from < -2 to < -3 SD

PMID: 28619046
- 1x proband with de novo fs
- head circumference was under 10th centle
Sources: Expert list
Severe microcephaly v2.20 CSNK2A1 Zornitza Stark gene: CSNK2A1 was added
gene: CSNK2A1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to 29240241
Phenotypes for gene: CSNK2A1 were set to Okur-Chung neurodevelopmental syndrome MIM#617062
Review for gene: CSNK2A1 was set to GREEN
gene: CSNK2A1 was marked as current diagnostic
Added comment: Microcephaly is a feature of the condition in 8/14 cases with de novo variants.
Sources: Expert list
Severe microcephaly v2.20 CHAMP1 Zornitza Stark gene: CHAMP1 was added
gene: CHAMP1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: CHAMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAMP1 were set to 27148580; 26340335
Phenotypes for gene: CHAMP1 were set to Mental retardation, autosomal dominant 40 (MIM#616579)
Review for gene: CHAMP1 was set to GREEN
gene: CHAMP1 was marked as current diagnostic
Added comment: PMID: 27148580;
- 10 patients including 5 from Hempel et al (PMID: 26340335)
- 7 with microcephaly defined as <3rd centile
- all PTVs and de novo

PMID: 26340335;
- 5 unrelated patients OFC at birth ranges from -0.4 to -3.1 SD
Sources: Expert list
Severe microcephaly v2.20 CEP63 Zornitza Stark reviewed gene: CEP63: Rating: AMBER; Mode of pathogenicity: None; Publications: 21983783, 26158450; Phenotypes: Seckel syndrome 6, MIM#614728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.20 BUB1B Zornitza Stark gene: BUB1B was added
gene: BUB1B was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: BUB1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1B were set to 18548531
Phenotypes for gene: BUB1B were set to Mosaic variegated aneuploidy syndrome 1 (MIM#257300)
Review for gene: BUB1B was set to GREEN
gene: BUB1B was marked as current diagnostic
Added comment: Severe microcephaly is a feature of MVAS. PMID: 18548531: review of 13 families with 12 presenting with microcephaly
Sources: Expert list
Severe microcephaly v2.20 BPTF Zornitza Stark gene: BPTF was added
gene: BPTF was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: BPTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BPTF were set to 28942966
Phenotypes for gene: BPTF were set to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM# 617755
Review for gene: BPTF was set to GREEN
gene: BPTF was marked as current diagnostic
Added comment: Microcephaly observed in 7/9 individuals reported.
Sources: Expert list
Severe microcephaly v2.20 AARS Zornitza Stark gene: AARS was added
gene: AARS was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: AARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS were set to 28493438; 25817015
Phenotypes for gene: AARS were set to Epileptic encephalopathy, early infantile, 29, MIM# 616339
Review for gene: AARS was set to GREEN
gene: AARS was marked as current diagnostic
Added comment: Bi-allelic variants associated with a severe phenotype comprising leukodystrophy, epilepsy, microcephaly and neurodevelopmental delay reported in three families.
Sources: Expert list
Severe microcephaly v2.20 FOXG1 Zornitza Stark gene: FOXG1 was added
gene: FOXG1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXG1 were set to 21441262; 19564653; 19578037
Phenotypes for gene: FOXG1 were set to Rett syndrome, congenital variant, MIM# 613454
Review for gene: FOXG1 was set to GREEN
gene: FOXG1 was marked as current diagnostic
Added comment: More than 20 individuals reported with de novo variants in this gene. Microcephaly is part of the phenotype.
Sources: Expert list
Severe microcephaly v2.20 EXOC7 Zornitza Stark gene: EXOC7 was added
gene: EXOC7 was added to Severe microcephaly. Sources: Expert list
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.
Sources: Expert list
Severe microcephaly v2.20 EIF2S3 Zornitza Stark gene: EIF2S3 was added
gene: EIF2S3 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: EIF2S3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EIF2S3 were set to 23063529; 27333055; 28055140; 32799315
Phenotypes for gene: EIF2S3 were set to MEHMO syndrome, MIM# 300148
Review for gene: EIF2S3 was set to GREEN
Added comment: 9 families reported (3 had the same variant) with MEHMO syndrome (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity).
Sources: Expert list
Severe microcephaly v2.20 TRAPPC9 Zornitza Stark gene: TRAPPC9 was added
gene: TRAPPC9 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC9 were set to 22549410; 20004765; 20004763; 30853973
Phenotypes for gene: TRAPPC9 were set to Mental retardation, autosomal recessive 13, MIM# 613192
Review for gene: TRAPPC9 was set to GREEN
gene: TRAPPC9 was marked as current diagnostic
Added comment: Microcephaly is part of the phenotype.
Sources: Expert list
Severe microcephaly v2.20 TRAPPC6B Zornitza Stark gene: TRAPPC6B was added
gene: TRAPPC6B was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TRAPPC6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC6B were set to 28626029; 28397838; 31687267
Phenotypes for gene: TRAPPC6B were set to Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862
Review for gene: TRAPPC6B was set to GREEN
gene: TRAPPC6B was marked as current diagnostic
Added comment: Five unrelated families reported with autosomal recessive neurodegenerative disorder characterised by global developmental delay, severe intellectual disability with poor or absent speech and autistic stereotypic behaviors, microcephaly, early-onset generalized seizures, and hypotonia.
Sources: Expert list
Severe microcephaly v2.20 TRAPPC12 Zornitza Stark gene: TRAPPC12 was added
gene: TRAPPC12 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TRAPPC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC12 were set to 32369837; 28777934
Phenotypes for gene: TRAPPC12 were set to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669
Review for gene: TRAPPC12 was set to GREEN
gene: TRAPPC12 was marked as current diagnostic
Added comment: Four families reported with a severe progressive encephalopathy characterized by microcephaly, global developmental delay, and hearing loss.
Sources: Expert list
Severe microcephaly v2.20 TPRKB Zornitza Stark gene: TPRKB was added
gene: TPRKB was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TPRKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPRKB were set to 28805828; 30053862
Phenotypes for gene: TPRKB were set to Galloway-Mowat syndrome 5, MIM# 617731
Review for gene: TPRKB was set to GREEN
gene: TPRKB was marked as current diagnostic
Added comment: Three unrelated families reported with renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly.
Sources: Expert list
Severe microcephaly v2.20 TP53RK Zornitza Stark gene: TP53RK was added
gene: TP53RK was added to Severe microcephaly. Sources: Expert Review
Mode of inheritance for gene: TP53RK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP53RK were set to 28805828; 30053862
Phenotypes for gene: TP53RK were set to Galloway-Mowat syndrome 4, MIM# 617730
Review for gene: TP53RK was set to GREEN
gene: TP53RK was marked as current diagnostic
Added comment: At least 4 unrelated families reported with renal-neurologic disease characterised by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most individuals have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable.
Sources: Expert Review
Severe microcephaly v2.20 TCF4 Zornitza Stark gene: TCF4 was added
gene: TCF4 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: TCF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCF4 were set to 18728071; 22934316
Phenotypes for gene: TCF4 were set to Pitt-Hopkins syndrome, MIM# 610954
Review for gene: TCF4 was set to GREEN
gene: TCF4 was marked as current diagnostic
Added comment: Well established gene-disease association. Microcephaly reported in around 60%.
Sources: Expert list
Severe microcephaly v2.20 SVBP Zornitza Stark gene: SVBP was added
gene: SVBP was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVBP were set to 31363758; 30607023
Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM #618569
Review for gene: SVBP was set to GREEN
Added comment: 5 unrelated families with homozygous mutations in SVBP, microcephaly is part of the phenotype. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Expert list
Severe microcephaly v2.20 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis
Review for gene: SMO was set to GREEN
gene: SMO was marked as current diagnostic
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Expert list
Severe microcephaly v2.20 SLC1A4 Zornitza Stark gene: SLC1A4 was added
gene: SLC1A4 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A4 were set to 25930971; 26138499; 26041762; 27193218; 29989513
Phenotypes for gene: SLC1A4 were set to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657
Review for gene: SLC1A4 was set to GREEN
Added comment: Spastic tetraplegia, thin corpus callosum, and progressive microcephaly is an autosomal recessive neurodevelopmental disorder characterized by onset of those features and severely impaired global development in early infancy. Most patients are unable to achieve independent walking or speech; some patients have seizures. Multiple affected families reported. Note founder variant p.Glu256Lys is a common founder variant in the Ashkenazi Jewish population.
Sources: Expert list
Severe microcephaly v2.20 SASS6 Zornitza Stark reviewed gene: SASS6: Rating: AMBER; Mode of pathogenicity: None; Publications: 24951542, 30639237; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.20 RUSC2 Zornitza Stark gene: RUSC2 was added
gene: RUSC2 was added to Severe microcephaly. 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
Severe microcephaly v2.20 PUS7 Zornitza Stark gene: PUS7 was added
gene: PUS7 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to 30526862; 30778726; 31583274
Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, OMIM #618342
Review for gene: PUS7 was set to GREEN
gene: PUS7 was marked as current diagnostic
Added comment: 11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.
Sources: Expert list
Severe microcephaly v2.20 PUF60 Zornitza Stark gene: PUF60 was added
gene: PUF60 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: PUF60 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUF60 were set to 28327570
Phenotypes for gene: PUF60 were set to Verheij syndrome, MIM# 615583
Review for gene: PUF60 was set to GREEN
gene: PUF60 was marked as current diagnostic
Added comment: Over 15 affected individuals reported. Short stature and dev delay are consistent features. 5/12 in the largest case series had microcephaly in relation to stature (Z-scores −2.48, −4.22, −2.09, −2.99, −2.53 respectively).
Sources: Expert list
Severe microcephaly v2.20 PTPN23 Zornitza Stark gene: PTPN23 was added
gene: PTPN23 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN23 were set to 31395947; 29899372; 29090338; 27848944; 25558065
Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Review for gene: PTPN23 was set to GREEN
Added comment: Over 10 families reported with an autosomal recessive neurologic disorder characterised by global developmental delay apparent from early infancy, poor overall growth often with microcephaly (6/10), impaired intellectual development with delayed or absent speech, axial hypotonia, and peripheral spasticity. Additional common but variable features include early-onset seizures, optic atrophy with poor visual fixation, and dysmorphic facial features. Brain imaging shows cerebral atrophy, poor or absent myelination with loss of white matter volume, and often hypoplasia of the corpus callosum and/or cerebellum.
Sources: Expert list
Severe microcephaly v2.20 PPP1R15B Zornitza Stark reviewed gene: PPP1R15B: Rating: AMBER; Mode of pathogenicity: None; Publications: 27640355; Phenotypes: Microcephaly, short stature, and impaired glucose metabolism 2, MIM# 616817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.20 POGZ Zornitza Stark gene: POGZ was added
gene: POGZ was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 26942287
Phenotypes for gene: POGZ were set to White-Sutton syndrome, MIM# 616364
Review for gene: POGZ was set to GREEN
gene: POGZ was marked as current diagnostic
Added comment: Microcephaly is reported in around half of affected individuals.
Sources: Expert list
Severe microcephaly v2.20 PDCD6IP Zornitza Stark gene: PDCD6IP was added
gene: PDCD6IP was added to Severe microcephaly. Sources: Expert list
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 Primary microcephaly
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. Borderline Red/Amber rating in view of the supportive animal model data.
Sources: Expert list
Severe microcephaly v2.20 DPP6 Zornitza Stark reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: None; Publications: 23832105; Phenotypes: Mental retardation, autosomal dominant 33 (MIM#616311); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v2.20 PCDH12 Zornitza Stark gene: PCDH12 was added
gene: PCDH12 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 27164683; 22822038; 30178464
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Review for gene: PCDH12 was set to GREEN
Added comment: Diencephalic-mesencephalic junction dysplasia syndrome-1 (DMJDS1) is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, severely delayed or even absent psychomotor development with profound intellectual disability, and spasticity or dystonia. Some patients may have seizures and/or visual impairment. Brain imaging shows a characteristic developmental malformation of the midbrain; subtle intracranial calcifications may also be present. At least 12 families reported.
Sources: Expert list
Severe microcephaly v2.20 ERCC5 Zornitza Stark edited their review of gene: ERCC5: Changed publications: 32052936, 24700531
Severe microcephaly v2.20 ERCC5 Zornitza Stark reviewed gene: ERCC5: Rating: AMBER; Mode of pathogenicity: None; Publications: 32052936; Phenotypes: Cerebrooculofacioskeletal syndrome 3 MIM#616570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.20 COASY Sebastian Lunke reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 28489334; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.20 ADARB1 Arina Puzriakova Publications for gene: ADARB1 were set to 32220291
Severe microcephaly v2.19 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
Severe microcephaly v2.19 HIST1H4C Zornitza Stark gene: HIST1H4C was added
gene: HIST1H4C was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: HIST1H4C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4C were set to 28920961
Phenotypes for gene: HIST1H4C were set to Growth delay, microcephaly and intellectual disability
Review for gene: HIST1H4C was set to GREEN
gene: HIST1H4C was marked as current diagnostic
Added comment: Two families and a zebrafish model reported initially, another case identified through clinical testing internally.
Sources: Expert list
Severe microcephaly v2.19 KIF14 Zornitza Stark gene: KIF14 was added
gene: KIF14 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to 28892560; 29343805
Phenotypes for gene: KIF14 were set to Microcephaly 20, primary, autosomal recessive, MIM# 617914
Review for gene: KIF14 was set to GREEN
gene: KIF14 was marked as current diagnostic
Added comment: At least 8 families reported. Microcephaly ranged from -3.6 to -11 SD.
Sources: Expert list
Severe microcephaly v2.19 LAGE3 Zornitza Stark edited their review of gene: LAGE3: Set current diagnostic: yes
Severe microcephaly v2.19 LAGE3 Zornitza Stark gene: LAGE3 was added
gene: LAGE3 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: LAGE3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: LAGE3 were set to 28805828
Phenotypes for gene: LAGE3 were set to Galloway-Mowat syndrome 2, X-linked, MIM# 301006
Review for gene: LAGE3 was set to GREEN
Added comment: Renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. At least three unrelated families and a mouse model.
Sources: Expert list
Severe microcephaly v2.19 OSGEP Zornitza Stark gene: OSGEP was added
gene: OSGEP was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: OSGEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OSGEP were set to 28805828; 28272532
Phenotypes for gene: OSGEP were set to Galloway-Mowat syndrome 3, MIM# 617729
Review for gene: OSGEP was set to GREEN
gene: OSGEP was marked as current diagnostic
Added comment: Early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most individuals have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Over 25 families reported.
Sources: Expert list
Severe microcephaly v2.19 NUP188 Zornitza Stark gene: NUP188 was added
gene: NUP188 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP188 were set to 32021605; 28726809; 32275884
Phenotypes for gene: NUP188 were set to microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Review for gene: NUP188 was set to GREEN
gene: NUP188 was marked as current diagnostic
Added comment: Eight unrelated individuals reported.
Sources: Expert list
Severe microcephaly v2.19 NUP107 Zornitza Stark gene: NUP107 was added
gene: NUP107 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: NUP107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP107 were set to 28280135; 28117080; 30179222; 25558065
Phenotypes for gene: NUP107 were set to Galloway-Mowat syndrome 7, MIM# 618348
Review for gene: NUP107 was set to GREEN
gene: NUP107 was marked as current diagnostic
Added comment: Autosomal recessive disorder characterised by developmental delay, microcephaly (-5 to -9 SD), and early-onset nephrotic syndrome. Approx 10 families reported. Recurrent variant p.Met101Ile identified in several families, likely represents a South Asian founder allele.
Sources: Expert list
Severe microcephaly v2.19 VRK1 Zornitza Stark gene: VRK1 was added
gene: VRK1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: VRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VRK1 were set to 19646678; 24126608; 27281532; 31560180
Phenotypes for gene: VRK1 were set to Pontocerebellar hypoplasia type 1A MIM#607596
Review for gene: VRK1 was set to GREEN
gene: VRK1 was marked as current diagnostic
Added comment: PMID 19646678: A homozygous nonsense variant was identified in an affected Ashkenazi Jewish family with 3 individuals with SMA-PCH. 2 had severe microcephaly (-6SD at 5yo and -7.9SD at 19mo). The third was noted to be microcephalic but no figures given. PMID 24126608: "Three affected individuals from 2 unrelated families presented with a complex neuropathy phenotype characterized by axonal sensorimotor neuropathy and microcephaly". 2 sibs from one family had head circumference -4SD and -6SD and were chet for missense variants. The third unrelated individual was -6SD and hom for a nonsense variant. PMID 27281532: reports another individual with microcephaly but no details provided.
Sources: Expert list
Severe microcephaly v2.19 BRD4 Zornitza Stark gene: BRD4 was added
gene: BRD4 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRD4 were set to 29379197; 30302754
Phenotypes for gene: BRD4 were set to Cornelia de Lange-like syndrome
Review for gene: BRD4 was set to AMBER
Added comment: A mixture of evidence from SNVs and CNVs. Note the CNVs are large and only some individuals have documented OFC < -3SD.

PMID: 29379197;
- 4x patients reports however only 3 reported with occipitofrontal circumference of < -3 SD
- 1x microdeletion of 1.04Mb, 1x missense and 1x fs. All de novo

PMID: 30302754
- 1x proband with occipitofrontal circumference 28 cm (−2 SD)
- de novo interstitial deletion involving the short arm of a chromosome 19, 1.97 Mb in size, which included BRD4
Sources: Expert list
Severe microcephaly v2.19 WDR4 Zornitza Stark reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26416026, 28617965, 30079490, 29597095; Phenotypes: Galloway-Mowat syndrome 6 MIM#618347; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Severe microcephaly v2.19 WDR37 Zornitza Stark edited their review of gene: WDR37: Set current diagnostic: yes
Severe microcephaly v2.19 WDR37 Zornitza Stark gene: WDR37 was added
gene: WDR37 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR37 were set to 31327508; 31327510
Phenotypes for gene: WDR37 were set to Neurooculocardiogenitourinary syndrome MIM#618652
Review for gene: WDR37 was set to GREEN
Added comment: Summary: 7/9 individuals reported with neurooculocardiogenitourinary syndrome had microcephaly. 5 had measurements provided and were severe (-3SD).

PMID 31327510: 4 individuals with de novo missense variants reported, with Neurooculocardiogenitourinary syndrome. All four have microcephaly - 49.5cm at 21yo, 40.2cm at 22mo (-4.8SD), 47.4cm at 7.5yo.

PMID 31327508: 5 probands with de novo missense variants, 3 with microcephaly (0th centile, <3rd centile (-5SD), and 11th centile)
Sources: Expert list
Severe microcephaly v2.19 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP1A2 were set to 30690204; 31608932
Phenotypes for gene: ATP1A2 were set to hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations
Review for gene: ATP1A2 was set to GREEN
gene: ATP1A2 was marked as current diagnostic
Added comment: This is a distinct phenotype from the one associated with mono-allelic variants.

PMID: 30690204;
- 2 families with severe microcephaly (-6 to -8 SD)
- both homozygous PTVs

PMID: 31608932;
- 4 patients from 2 families
- Family A, all 3 affecteds had severe microcephaly during ultrasound (-3 to -4 SD)
- Family B, no measurements were reported
- both homozygous PTVs
Sources: Expert list
Severe microcephaly v2.19 ARCN1 Zornitza Stark gene: ARCN1 was added
gene: ARCN1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: ARCN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARCN1 were set to 27476655
Phenotypes for gene: ARCN1 were set to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164)
Review for gene: ARCN1 was set to GREEN
gene: ARCN1 was marked as current diagnostic
Added comment: Borderline Amber/Green. Microcephaly is a key part of the phenotype but few exact measurements actually reported.
Sources: Expert list
Severe microcephaly v2.19 AP4S1 Zornitza Stark gene: AP4S1 was added
gene: AP4S1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: AP4S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4S1 were set to 21620353; 25552650; 27444738
Phenotypes for gene: AP4S1 were set to Spastic paraplegia 52, autosomal recessive (MIM#614067)
Review for gene: AP4S1 was set to GREEN
gene: AP4S1 was marked as current diagnostic
Added comment: Borderline Amber/Green as only one affected individual <-3SD; however, part of same gene family as other spastic paraplegias with microcephaly. Microcephaly in another family -2SD and precise information on the microcephaly not available for third family.
Sources: Expert list
Severe microcephaly v2.19 AP4M1 Zornitza Stark gene: AP4M1 was added
gene: AP4M1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: AP4M1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4M1 were set to 28464862; 24700674
Phenotypes for gene: AP4M1 were set to Spastic paraplegia 50, autosomal recessive (MIM#612936)
Review for gene: AP4M1 was set to GREEN
gene: AP4M1 was marked as current diagnostic
Added comment: Despite the OMIM name, this is a complex neurological condition, where microcephaly is an early prominent presenting feature.

PMID: 28464862;
- 1x with severe progressive microcephaly (< - 4 SD)
- homozygous nonsense

PMID: 24700674;
- 2x unrelated patients (1 and 3) < -3 SD head circumference
- 2x homozygous nonsense
Sources: Expert list
Severe microcephaly v2.19 NSD2 Zornitza Stark gene: NSD2 was added
gene: NSD2 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: NSD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD2 were set to 30345613; 31171569
Phenotypes for gene: NSD2 were set to microcephaly; intellectual disability
Review for gene: NSD2 was set to GREEN
Added comment: Microcephaly reported in 6 of 7 individuals with LOF variants in this gene.
Sources: Expert list
Severe microcephaly v2.19 ZNF335 Zornitza Stark reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 23178126, 27540107, 29652087; Phenotypes: Microcephaly 10, primary, autosomal recessive (MIM#615095); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Severe microcephaly v2.19 MED17 Zornitza Stark gene: MED17 was added
gene: MED17 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: MED17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED17 were set to 20950787; 30345598; 26004231
Phenotypes for gene: MED17 were set to Microcephaly, postnatal progressive, with seizures and brain atrophy, MIM# 613668
Review for gene: MED17 was set to GREEN
gene: MED17 was marked as current diagnostic
Added comment: Five individuals from four families reported initially, founder effect for p.Leu371Pro. Two additional families reported since with different variants, one family with milder phenotype.
Sources: Expert list
Severe microcephaly v2.19 MECP2 Zornitza Stark gene: MECP2 was added
gene: MECP2 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: MECP2 were set to Rett syndrome, MIM# 312750; Encephalopathy, neonatal severe 300673
Review for gene: MECP2 was set to GREEN
gene: MECP2 was marked as current diagnostic
Added comment: Well established gene-disease association, microcephaly is a key phenotypic feature both in Rett syndrome and in males affected by severe neonatal encephalopathy.
Sources: Expert list
Severe microcephaly v2.19 AKT3 Zornitza Stark changed review comment from: Activating variants in AKT2 and micro duplications are associated with macrocephaly/megalencephaly. Note that deletions involving AKT3 have consistently been associated with microcephaly. However, most involve at least one other gene apart from AKT3. One family reported with only AKT3 deleted: deletion was inherited from a phenotypically normal parent, suggesting either additional effects in bigger deletions or incomplete penetrance. You may wish to consider adding the CNV region to this panel rather than AKT3 alone, in which case I suspect the region has enough evidence for a Green rating.
Sources: Expert list; to: Activating variants in AKT3 and micro duplications are associated with macrocephaly/megalencephaly. Note that deletions involving AKT3 have consistently been associated with microcephaly. However, most involve at least one other gene apart from AKT3. One family reported with only AKT3 deleted: deletion was inherited from a phenotypically normal parent, suggesting either additional effects in bigger deletions or incomplete penetrance. You may wish to consider adding the CNV region to this panel rather than AKT3 alone, in which case I suspect the region has enough evidence for a Green rating.
Sources: Expert list
Severe microcephaly v2.19 AKT3 Zornitza Stark gene: AKT3 was added
gene: AKT3 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to 32827175; 31929334; 30853971; 30053339; 25424989
Phenotypes for gene: AKT3 were set to Microcephaly
Review for gene: AKT3 was set to AMBER
Added comment: Activating variants in AKT2 and micro duplications are associated with macrocephaly/megalencephaly. Note that deletions involving AKT3 have consistently been associated with microcephaly. However, most involve at least one other gene apart from AKT3. One family reported with only AKT3 deleted: deletion was inherited from a phenotypically normal parent, suggesting either additional effects in bigger deletions or incomplete penetrance. You may wish to consider adding the CNV region to this panel rather than AKT3 alone, in which case I suspect the region has enough evidence for a Green rating.
Sources: Expert list
Severe microcephaly v2.19 AP4E1 Zornitza Stark gene: AP4E1 was added
gene: AP4E1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: AP4E1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4E1 were set to 20972249; 21620353; 21937992
Phenotypes for gene: AP4E1 were set to Spastic paraplegia 51, autosomal recessive, MIM# 613744
Review for gene: AP4E1 was set to GREEN
gene: AP4E1 was marked as current diagnostic
Added comment: Autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development. Microcephaly is a prominent, presenting feature. At least 3 families reported.
Sources: Expert list
Severe microcephaly v2.19 AP4B1 Zornitza Stark gene: AP4B1 was added
gene: AP4B1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4B1 were set to 21620353; 22290197; 24700674; 24781758
Phenotypes for gene: AP4B1 were set to Spastic paraplegia 47, autosomal recessive, MIM# 614066
Review for gene: AP4B1 was set to GREEN
gene: AP4B1 was marked as current diagnostic
Added comment: Microcephaly is an early, prominent presenting feature of this progressive neurological disorder. At least 4 unrelated families reported.
Sources: Expert list
Severe microcephaly v2.19 ANKLE2 Zornitza Stark edited their review of gene: ANKLE2: Changed rating: GREEN
Severe microcephaly v2.19 ANKLE2 Zornitza Stark reviewed gene: ANKLE2: Rating: ; Mode of pathogenicity: None; Publications: 25259927, 30214071, 31735666; Phenotypes: Microcephaly 16, primary, autosomal recessive, MIM# 616681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Severe microcephaly v2.19 AGMO Zornitza Stark reviewed gene: AGMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 31555905; Phenotypes: microcephaly, intellectual disability, epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Severe microcephaly v2.19 TUBGCP2 Arina Puzriakova Classified gene: TUBGCP2 as Amber List (moderate evidence)
Severe microcephaly v2.19 TUBGCP2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least three families with distinct TUBGCP2 variants, presenting progressive severe microcephaly.
Severe microcephaly v2.19 TUBGCP2 Arina Puzriakova Gene: tubgcp2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.18 TUBGCP2 Arina Puzriakova gene: TUBGCP2 was added
gene: TUBGCP2 was added to Severe microcephaly. Sources: Literature
for-review tags were added to gene: TUBGCP2.
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to 31630790
Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737
Review for gene: TUBGCP2 was set to GREEN
Added comment: Associated with phenotype in OMIM, and a probable gene for Microcephaly and Lissencephaly Spectrum Disorders in G2P.

PMID: 31630790 (2019) - Five patients from four families with biallelic variants in the TUBGCP2 gene. Affected individuals shared phenotypic features that included progressive severe microcephaly (4/4, Z score: -4.0 to -9.0), developmental delay (5/5, mild-severe), seizures (4/5). All patients exhibited lissencephaly-spectrum phenotypes with varying degrees of cortical malformations on brain imaging including pachygyria and subcortical band heterotopia.

All variants segregated with disease in each family. Analysis of fibroblasts derived from one patient with a splice site variant revealed several abnormal transcripts, predicted to result in LoF. No further functional studies of other variants or patient cells were performed.
Sources: Literature
Severe microcephaly v2.17 NCAPH Arina Puzriakova Tag watchlist tag was added to gene: NCAPH.
Severe microcephaly v2.17 NCAPH Arina Puzriakova Classified gene: NCAPH as Red List (low evidence)
Severe microcephaly v2.17 NCAPH Arina Puzriakova Added comment: Comment on list classification: Additional cases are required to substantiate causation but added to watchlist.
Severe microcephaly v2.17 NCAPH Arina Puzriakova Gene: ncaph has been classified as Red List (Low Evidence).
Severe microcephaly v2.16 NCAPH Arina Puzriakova gene: NCAPH was added
gene: NCAPH was added to Severe microcephaly. Sources: Literature
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
Severe microcephaly v2.15 NCAPD3 Arina Puzriakova Classified gene: NCAPD3 as Amber List (moderate evidence)
Severe microcephaly v2.15 NCAPD3 Arina Puzriakova Added comment: Comment on list classification: Additional cases, as well as a more significant pattern of microcephaly, are required before inclusion of NCAPD3 on a diagnostic panel.
Severe microcephaly v2.15 NCAPD3 Arina Puzriakova Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.14 NCAPD3 Arina Puzriakova gene: NCAPD3 was added
gene: NCAPD3 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: NCAPD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPD3 were set to 27737959
Phenotypes for gene: NCAPD3 were set to Microcephaly 22, primary, autosomal recessive, 617984
Review for gene: NCAPD3 was set to AMBER
Added comment: Associated with Microcephaly 22 in OMIM and a possible gene for Microcephaly with short stature in G2P.

PMID: 27737959 (2016) - Two unrelated cases. Compound heterozygous variants ([c.1783_1784delG, p.Val595Serfs*34];[c.382+14A>G, p.Ser129Metfs*1]) were detected in a 6-years-5-month-old male with microcephaly (OFC -5.4 SD). The second patient (aged 6-years-11-months-old) was less severely microcephalic (OFC -2.7 SD) but additionally had moderate developmental delay, seizures and lower limb hypertonia, and also harboured a homozygous missense variant in NCAPD3 (c.3458T>G, p.Glu1153Ala).

Functional studies indicated that both variants 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
Severe microcephaly v2.13 NCAPD2 Arina Puzriakova Tag for-review tag was added to gene: NCAPD2.
Severe microcephaly v2.13 NCAPD2 Arina Puzriakova Classified gene: NCAPD2 as Amber List (moderate evidence)
Severe microcephaly v2.13 NCAPD2 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 three unrelated pedigrees with the relevant phenotype.
Severe microcephaly v2.13 NCAPD2 Arina Puzriakova Gene: ncapd2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.12 NCAPD2 Arina Puzriakova gene: NCAPD2 was added
gene: NCAPD2 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPD2 were set to 27737959; 28097321; 31056748
Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive, 617983
Review for gene: NCAPD2 was set to GREEN
Added comment: Associated with phenotype in OMIM and a possible gene for Microcephaly with short stature in G2P.

PMID: 27737959 (2016) - A homozygous splice site variant (c.4120+2T>C, p.Asp1374Glyfs*29) in NCAPD2 was detected in a 3-year-old male with severe microcephaly (OFC -11.9 SD), severe ID, autistic-like behaviours, and no speech. The variant was found in a heterozygous state in both unaffected parents and was not present in the ExAC database. Functional studies indicated that the variant disrupted condensin-dependent mitotic chromosome integrity, providing supporting evidence for pathogenicity.

PMID: 28097321 (2017) - In two affected cousins from a consanguineous family with mild ID, intrauterine growth retardation, short stature, and microcephaly. Homozygous missense variants were found in NCAPD2 (c.23T>C, p.Phe8Ser), but also in ENO2 (c.710C>T, p.Thr237Met). Variants segregated with disease in the family, but no further functional studies were undertaken of the variants or patient cells.

PMID: 31056748 (2019) - In a 13-year-old female with severe microcephaly (OFC < -3), mild ID (IQ 59), poor learning performance, sloping forehead and reduced cerebral cortex size, exome sequencing revealed a homozygous variant in NCAPD2 (c.3477+2T>C, p.Gly1160Valfs*16). Progressive microcephaly was also apparent in a sibling of the proband, a male fetus which was terminated at 34 weeks of pregnancy. The same homozygous variant was identified in the fetus, while parents were heterozygotes and an unaffected brother was homozygous for the other allele. No further functional studies of the variant or patient cells were performed.
Sources: Literature
Severe microcephaly v2.11 ADARB1 Arina Puzriakova changed review comment from: Variants reported in four unrelated individuals with severe/profound intellectual disability, microcephaly, and seizures. Affected individuals were microcephalic at birth or developed postnatal microcephaly ranging from -3.6 to -4.0 SD. 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.
Sources: Literature; 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 Intellectual Disability panels with a suggested Green classification at the next major review.
Severe microcephaly v2.11 ADARB1 Sarah Leigh Tag for-review tag was added to gene: ADARB1.
Severe microcephaly v2.11 ADARB1 Sarah Leigh Classified gene: ADARB1 as Amber List (moderate evidence)
Severe microcephaly v2.11 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.
Severe microcephaly v2.11 ADARB1 Sarah Leigh Gene: adarb1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.10 ADARB1 Arina Puzriakova gene: ADARB1 was added
gene: ADARB1 was added to Severe microcephaly. 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 Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862
Review for gene: ADARB1 was set to GREEN
Added comment: Variants reported in four unrelated individuals with severe/profound intellectual disability, microcephaly, and seizures. Affected individuals were microcephalic at birth or developed postnatal microcephaly ranging from -3.6 to -4.0 SD. 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.
Sources: Literature
Severe microcephaly v2.10 TTC5 Sarah Leigh commented on gene: TTC5: There is enough evidence for this gene to be rated GREEN at the next major review.
Severe microcephaly v2.10 TTC5 Sarah Leigh commented on gene: TTC5: There is enough evidence for this gene to be rated GREEN at the next major review.
Severe microcephaly v2.10 TTC5 Sarah Leigh Classified gene: TTC5 as Amber List (moderate evidence)
Severe microcephaly v2.10 TTC5 Sarah Leigh Gene: ttc5 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.9 TTC5 Sarah Leigh gene: TTC5 was added
gene: TTC5 was added to Severe microcephaly. Sources: Literature
for-review tags were added to gene: TTC5.
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
Review for gene: TTC5 was set to GREEN
Added comment: 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.
Sources: Literature
Severe microcephaly v2.8 TMX2 Sarah Leigh Classified gene: TMX2 as Green List (high evidence)
Severe microcephaly v2.8 TMX2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Primary microcephaly, cortical malformation and epileptic encephalopathy. At least 7 variants reported in at least 9 unrelated cases of Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730 (PMID 31735293; 31270415).
Severe microcephaly v2.8 TMX2 Sarah Leigh Gene: tmx2 has been classified as Green List (High Evidence).
Severe microcephaly v2.7 TMX2 Sarah Leigh gene: TMX2 was added
gene: TMX2 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMX2 were set to 31586943; 31735293; 31270415
Phenotypes for gene: TMX2 were set to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730
Review for gene: TMX2 was set to GREEN
Added comment: Sources: Literature
Severe microcephaly v2.6 C7orf43 Zornitza Stark gene: C7orf43 was added
gene: C7orf43 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Review for gene: C7orf43 was set to AMBER
Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model. HGNC approved name: MAP11.
Sources: Literature
Severe microcephaly v2.6 CEP55 Rebecca Foulger Classified gene: CEP55 as Green List (high evidence)
Severe microcephaly v2.6 CEP55 Rebecca Foulger Gene: cep55 has been classified as Green List (High Evidence).
Severe microcephaly v2.5 CEP55 Rebecca Foulger changed review comment from: PMID:32100459 (Barrie et al., 2020) describe 7 living indivduals (5 families) with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all have a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings are homozygous for a consensus splice site variant near the end of the gene. These affected girls all have severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. The authors suggest that individuals compound het for missense + nonsense variants in CEP55 have a viable phenotype (compared to lethal MARCH phenotype).; to: PMID:32100459 (Barrie et al., 2020) describe 7 living indivduals (5 families) with biallelic CEP55 variants (compound het, or homozygous splice site variant). Three sisters (Patients 5,6,7) have severe microcephaly (-7.1 SD, -5.5, -5.5). An additional 3 unrelated patients (Patients 1,2,3) have microcephaly scores of -2 SD, -2.7 SD, and Patient 4 has borderline microcephaly. Severe microcephaly (NHS Test Directory) is defined as having an occipitofrontal circumference (OFC) beyond 3 standard deviations below the mean for age. There are 4 unrelated cases which meet this threshold (3 sisters) or are close to this threshold (3 unrelated patients) and therefore on balance have rated as Green awaiting further GLH review.
Severe microcephaly v2.5 CEP55 Rebecca Foulger commented on gene: CEP55: PMID:32100459 (Barrie et al., 2020) describe 7 living indivduals (5 families) with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all have a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings are homozygous for a consensus splice site variant near the end of the gene. These affected girls all have severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. The authors suggest that individuals compound het for missense + nonsense variants in CEP55 have a viable phenotype (compared to lethal MARCH phenotype).
Severe microcephaly v2.5 CEP55 Rebecca Foulger gene: CEP55 was added
gene: CEP55 was added to Severe microcephaly. 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, speech delays, and bilateral toe syndactyly
Review for gene: CEP55 was set to GREEN
Added comment: Added to Microcephaly panel on advice from Helen Brittain, Genomics England Clinical Team. Phenotype of living individuals described in PMID:32100459 (Barrie et al., 2020) includes microcephaly.
Sources: Literature
Severe microcephaly v2.3 Catherine Snow Panel version has been signed off
Severe microcephaly v2.0 Louise Daugherty promoted panel to version 2.0
Severe microcephaly v1.79 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Severe microcephaly v1.78 ZNHIT3 Louise Daugherty edited their review of gene: ZNHIT3: Added comment: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; Changed rating: RED
Severe microcephaly v1.78 UFC1 Louise Daugherty Classified gene: UFC1 as Green List (high evidence)
Severe microcephaly v1.78 UFC1 Louise Daugherty Added comment: Comment on list classification: Gene rated Green- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature
Severe microcephaly v1.78 UFC1 Louise Daugherty Gene: ufc1 has been classified as Green List (High Evidence).
Severe microcephaly v1.77 UFM1 Louise Daugherty commented on gene: UFM1: Gene rated Green this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature
Severe microcephaly v1.77 UBA5 Louise Daugherty Deleted their comment
Severe microcephaly v1.77 UBA5 Louise Daugherty Classified gene: UBA5 as Green List (high evidence)
Severe microcephaly v1.77 UBA5 Louise Daugherty Added comment: Comment on list classification: Gene rated Green- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature
Severe microcephaly v1.77 UBA5 Louise Daugherty Gene: uba5 has been classified as Green List (High Evidence).
Severe microcephaly v1.76 UBA5 Louise Daugherty changed review comment from: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; to: Gene rated Green- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature
Severe microcephaly v1.76 UBA5 Louise Daugherty edited their review of gene: UBA5: Changed rating: GREEN
Severe microcephaly v1.76 UBA5 Louise Daugherty edited their review of gene: UBA5: Added comment: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; Changed rating: RED
Severe microcephaly v1.76 CCDC88A Louise Daugherty edited their review of gene: CCDC88A: Changed rating: AMBER
Severe microcephaly v1.76 PCLO Louise Daugherty edited their review of gene: PCLO: Added comment: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; Changed rating: RED
Severe microcephaly v1.76 CCDC88A Louise Daugherty Publications for gene: CCDC88A were set to
Severe microcephaly v1.75 CCDC88A Louise Daugherty Classified gene: CCDC88A as Amber List (moderate evidence)
Severe microcephaly v1.75 CCDC88A Louise Daugherty Added comment: Comment on list classification: Gene rated Amber- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature
Severe microcephaly v1.75 CCDC88A Louise Daugherty Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Severe microcephaly v1.74 UFC1 Helen Brittain reviewed gene: UFC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 29868776; Phenotypes: Neurodevelopmental disorder with spasticity and poor growth, 618076; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.74 ZNHIT3 Helen Brittain reviewed gene: ZNHIT3: Rating: RED; Mode of pathogenicity: ; Publications: 28335020; Phenotypes: PEHO syndrome, 260565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.74 PCLO Helen Brittain reviewed gene: PCLO: Rating: RED; Mode of pathogenicity: ; Publications: 25832664; Phenotypes: ?Pontocerebellar hypoplasia, type 3, 608027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.74 UFM1 Helen Brittain reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28931644, 29868776, 27545674; Phenotypes: Leukodystrophy, hypomyelinating, 14, 617899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.74 UBA5 Helen Brittain reviewed gene: UBA5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 44, 617132; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.74 CCDC88A Helen Brittain reviewed gene: CCDC88A: Rating: AMBER; Mode of pathogenicity: ; Publications: 26917597, 30392057; Phenotypes: ?PEHO syndrome-like, 617507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v1.73 Louise Daugherty List of related panels changed from Primary Microcephaly - Microcephalic Dwarfism Spectrum; Severe microcephaly to Primary Microcephaly - Microcephalic Dwarfism Spectrum; Severe microcephaly; R88
Severe microcephaly v1.72 KIF1BP Louise Daugherty Tag new-gene-name tag was added to gene: KIF1BP.
Severe microcephaly v1.72 KIF1BP Louise Daugherty commented on gene: KIF1BP: Added new-gene-name tag, new approved HGNC gene symbol for KIF1BP is KIFBP
Severe microcephaly v1.72 IARS Louise Daugherty commented on gene: IARS: Added new-gene-name tag, new approved HGNC gene symbol for IARS is IARS1
Severe microcephaly v1.72 QARS Louise Daugherty Tag new-gene-name tag was added to gene: QARS.
Severe microcephaly v1.72 QARS Louise Daugherty commented on gene: QARS: Added new-gene-name tag, new approved HGNC gene symbol for QARS is QARS1
Severe microcephaly v1.72 UFC1 Louise Daugherty Added comment: Comment on publications: review from Geoff Woods: 5 families reported in PMID 30552426 and 29868776
Severe microcephaly v1.72 UFC1 Louise Daugherty Publications for gene: UFC1 were set to 26917597
Severe microcephaly v1.71 ZNHIT3 Louise Daugherty Publications for gene: ZNHIT3 were set to
Severe microcephaly v1.70 PCLO Louise Daugherty Publications for gene: PCLO were set to
Severe microcephaly v1.69 UBA5 Louise Daugherty Publications for gene: UBA5 were set to
Severe microcephaly v1.68 UFC1 Louise Daugherty Publications for gene: UFC1 were set to
Severe microcephaly v1.67 IARS Sarah Leigh Tag new-gene-name tag was added to gene: IARS.
Severe microcephaly v1.67 IARS Sarah Leigh commented on gene: IARS
Severe microcephaly v1.67 ISCA-37501-Loss Louise Daugherty Source NHS GMS was added to Region: ISCA-37501-Loss.
Severe microcephaly v1.66 ISCA-37425-Gain Louise Daugherty Haploinsufficiency Score for ISCA-37425-Gain was changed from to None.
Source NHS GMS was added to Region: ISCA-37425-Gain.
Severe microcephaly v1.65 ISCA-37408-Loss Louise Daugherty Triplosensitivity Score for ISCA-37408-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37408-Loss.
Severe microcephaly v1.64 ISCA-37406-Loss Louise Daugherty Triplosensitivity Score for ISCA-37406-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37406-Loss.
Severe microcephaly v1.63 ISCA-37390-Loss Louise Daugherty Triplosensitivity Score for ISCA-37390-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37390-Loss.
Severe microcephaly v1.62 ISCA-37390-Loss Louise Daugherty reviewed Region: ISCA-37390-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v1.62 ISCA-37406-Loss Louise Daugherty reviewed Region: ISCA-37406-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v1.62 ISCA-37408-Loss Louise Daugherty reviewed Region: ISCA-37408-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v1.62 ISCA-37425-Gain Louise Daugherty reviewed Region: ISCA-37425-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v1.62 ISCA-37501-Loss Louise Daugherty commented on Region: ISCA-37501-Loss: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this region Green
Severe microcephaly v1.62 WDFY3 Louise Daugherty reviewed gene: WDFY3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TUBGCP3 Louise Daugherty reviewed gene: TUBGCP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TRMT1 Louise Daugherty reviewed gene: TRMT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 SASS6 Louise Daugherty reviewed gene: SASS6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PPP1R15B Louise Daugherty reviewed gene: PPP1R15B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PLAA Louise Daugherty reviewed gene: PLAA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PHC1 Louise Daugherty reviewed gene: PHC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 NSMCE2 Louise Daugherty reviewed gene: NSMCE2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 NIN Louise Daugherty reviewed gene: NIN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCM Louise Daugherty reviewed gene: FANCM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ERCC5 Louise Daugherty reviewed gene: ERCC5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 EOMES Louise Daugherty reviewed gene: EOMES: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DNA2 Louise Daugherty reviewed gene: DNA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CENPE Louise Daugherty reviewed gene: CENPE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CDK6 Louise Daugherty reviewed gene: CDK6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CDC6 Louise Daugherty reviewed gene: CDC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ATRIP Louise Daugherty reviewed gene: ATRIP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ANKLE2 Louise Daugherty reviewed gene: ANKLE2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 AGMO Louise Daugherty reviewed gene: AGMO: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ZNF335 Louise Daugherty reviewed gene: ZNF335: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 WDR4 Louise Daugherty edited their review of gene: WDR4: Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber; Changed rating: AMBER
Severe microcephaly v1.62 TAF13 Louise Daugherty reviewed gene: TAF13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RMI1 Louise Daugherty reviewed gene: RMI1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RAD51C Louise Daugherty reviewed gene: RAD51C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 QARS Louise Daugherty reviewed gene: QARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 MRE11 Louise Daugherty commented on gene: MRE11: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Severe microcephaly v1.62 CRIPT Louise Daugherty reviewed gene: CRIPT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 COASY Louise Daugherty commented on gene: COASY: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Severe microcephaly v1.62 ZEB2 Louise Daugherty reviewed gene: ZEB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 XRCC4 Louise Daugherty reviewed gene: XRCC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 WDR73 Louise Daugherty reviewed gene: WDR73: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 WDR62 Louise Daugherty reviewed gene: WDR62: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TUBGCP6 Louise Daugherty reviewed gene: TUBGCP6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TUBGCP4 Louise Daugherty reviewed gene: TUBGCP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TRMT10A Louise Daugherty reviewed gene: TRMT10A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TRAIP Louise Daugherty reviewed gene: TRAIP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 TOP3A Louise Daugherty reviewed gene: TOP3A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 STIL Louise Daugherty reviewed gene: STIL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 STAMBP Louise Daugherty reviewed gene: STAMBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 SMC3 Louise Daugherty reviewed gene: SMC3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 SMC1A Louise Daugherty reviewed gene: SMC1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 SLX4 Louise Daugherty reviewed gene: SLX4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 SLC9A6 Louise Daugherty reviewed gene: SLC9A6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 SLC25A19 Louise Daugherty reviewed gene: SLC25A19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RTTN Louise Daugherty reviewed gene: RTTN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RPL10 Louise Daugherty reviewed gene: RPL10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RNU4ATAC Louise Daugherty reviewed gene: RNU4ATAC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RBBP8 Louise Daugherty reviewed gene: RBBP8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 RAD21 Louise Daugherty reviewed gene: RAD21: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PQBP1 Louise Daugherty reviewed gene: PQBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 POC1A Louise Daugherty reviewed gene: POC1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PNKP Louise Daugherty reviewed gene: PNKP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PLK4 Louise Daugherty reviewed gene: PLK4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PDHA1 Louise Daugherty reviewed gene: PDHA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PCNT Louise Daugherty reviewed gene: PCNT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PALB2 Louise Daugherty reviewed gene: PALB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ORC6 Louise Daugherty reviewed gene: ORC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ORC4 Louise Daugherty reviewed gene: ORC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ORC1 Louise Daugherty reviewed gene: ORC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 NIPBL Louise Daugherty reviewed gene: NIPBL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 NHEJ1 Louise Daugherty reviewed gene: NHEJ1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 NDE1 Louise Daugherty reviewed gene: NDE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 NBN Louise Daugherty reviewed gene: NBN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 MYCN Louise Daugherty reviewed gene: MYCN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 MSMO1 Louise Daugherty reviewed gene: MSMO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 MFSD2A Louise Daugherty reviewed gene: MFSD2A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 MCPH1 Louise Daugherty reviewed gene: MCPH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 LIG4 Louise Daugherty reviewed gene: LIG4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 LARP7 Louise Daugherty reviewed gene: LARP7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 KIF11 Louise Daugherty reviewed gene: KIF11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 IGF1R Louise Daugherty reviewed gene: IGF1R: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 IGF1 Louise Daugherty reviewed gene: IGF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 IER3IP1 Louise Daugherty reviewed gene: IER3IP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 IARS Louise Daugherty edited their review of gene: IARS: Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green; Changed rating: AMBER
Severe microcephaly v1.62 HDAC8 Louise Daugherty reviewed gene: HDAC8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 GMNN Louise Daugherty reviewed gene: GMNN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCL Louise Daugherty reviewed gene: FANCL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCI Louise Daugherty reviewed gene: FANCI: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCG Louise Daugherty reviewed gene: FANCG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCF Louise Daugherty reviewed gene: FANCF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCE Louise Daugherty reviewed gene: FANCE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCD2 Louise Daugherty reviewed gene: FANCD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCC Louise Daugherty reviewed gene: FANCC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCB Louise Daugherty reviewed gene: FANCB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 FANCA Louise Daugherty reviewed gene: FANCA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ERCC8 Louise Daugherty reviewed gene: ERCC8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ERCC6 Louise Daugherty reviewed gene: ERCC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ERCC4 Louise Daugherty reviewed gene: ERCC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 EFTUD2 Louise Daugherty reviewed gene: EFTUD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DYRK1A Louise Daugherty reviewed gene: DYRK1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DPP6 Louise Daugherty reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DONSON Louise Daugherty reviewed gene: DONSON: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DIAPH1 Louise Daugherty reviewed gene: DIAPH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DHCR7 Louise Daugherty reviewed gene: DHCR7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 DDX11 Louise Daugherty reviewed gene: DDX11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CTNNB1 Louise Daugherty reviewed gene: CTNNB1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CREBBP Louise Daugherty reviewed gene: CREBBP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CKAP2L Louise Daugherty reviewed gene: CKAP2L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CIT Louise Daugherty reviewed gene: CIT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CEP63 Louise Daugherty reviewed gene: CEP63: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CEP152 Louise Daugherty reviewed gene: CEP152: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CEP135 Louise Daugherty reviewed gene: CEP135: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CENPJ Louise Daugherty reviewed gene: CENPJ: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CENPF Louise Daugherty reviewed gene: CENPF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CDT1 Louise Daugherty reviewed gene: CDT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CDK5RAP2 Louise Daugherty reviewed gene: CDK5RAP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 CASK Louise Daugherty reviewed gene: CASK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 BRIP1 Louise Daugherty reviewed gene: BRIP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 BRCA2 Louise Daugherty reviewed gene: BRCA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 BLM Louise Daugherty reviewed gene: BLM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ATRX Louise Daugherty reviewed gene: ATRX: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ATR Louise Daugherty reviewed gene: ATR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 ASPM Louise Daugherty reviewed gene: ASPM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 PRUNE1 Louise Daugherty reviewed gene: PRUNE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 KNL1 Louise Daugherty reviewed gene: KNL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.62 KIF1BP Louise Daugherty reviewed gene: KIF1BP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.61 UFC1 Louise Daugherty Source NHS GMS was added to UFC1.
Severe microcephaly v1.61 ZNHIT3 Louise Daugherty Source NHS GMS was added to ZNHIT3.
Severe microcephaly v1.61 PCLO Louise Daugherty Source NHS GMS was added to PCLO.
Severe microcephaly v1.61 UFM1 Louise Daugherty Source NHS GMS was added to UFM1.
Severe microcephaly v1.61 UBA5 Louise Daugherty Source NHS GMS was added to UBA5.
Severe microcephaly v1.61 CCDC88A Louise Daugherty Source NHS GMS was added to CCDC88A.
Severe microcephaly v1.61 WDFY3 Louise Daugherty Source NHS GMS was added to WDFY3.
Severe microcephaly v1.61 TUBGCP3 Louise Daugherty Source NHS GMS was added to TUBGCP3.
Severe microcephaly v1.61 TRMT1 Louise Daugherty Source NHS GMS was added to TRMT1.
Severe microcephaly v1.61 SASS6 Louise Daugherty Source NHS GMS was added to SASS6.
Severe microcephaly v1.61 PPP1R15B Louise Daugherty Source NHS GMS was added to PPP1R15B.
Severe microcephaly v1.61 PLAA Louise Daugherty Source NHS GMS was added to PLAA.
Severe microcephaly v1.61 PHC1 Louise Daugherty Source NHS GMS was added to PHC1.
Severe microcephaly v1.61 NSMCE2 Louise Daugherty Source NHS GMS was added to NSMCE2.
Severe microcephaly v1.61 NIN Louise Daugherty Source NHS GMS was added to NIN.
Severe microcephaly v1.61 FANCM Louise Daugherty Source NHS GMS was added to FANCM.
Severe microcephaly v1.61 ERCC5 Louise Daugherty Source NHS GMS was added to ERCC5.
Severe microcephaly v1.61 EOMES Louise Daugherty Source NHS GMS was added to EOMES.
Severe microcephaly v1.61 DNA2 Louise Daugherty Source NHS GMS was added to DNA2.
Severe microcephaly v1.61 CENPE Louise Daugherty Source NHS GMS was added to CENPE.
Severe microcephaly v1.61 CDK6 Louise Daugherty Source NHS GMS was added to CDK6.
Severe microcephaly v1.61 CDC6 Louise Daugherty Source NHS GMS was added to CDC6.
Severe microcephaly v1.61 ATRIP Louise Daugherty Source NHS GMS was added to ATRIP.
Severe microcephaly v1.61 ANKLE2 Louise Daugherty Source NHS GMS was added to ANKLE2.
Severe microcephaly v1.61 AGMO Louise Daugherty Source NHS GMS was added to AGMO.
Severe microcephaly v1.61 ZNF335 Louise Daugherty Source NHS GMS was added to ZNF335.
Severe microcephaly v1.61 WDR4 Louise Daugherty Source NHS GMS was added to WDR4.
Severe microcephaly v1.61 TAF13 Louise Daugherty Source NHS GMS was added to TAF13.
Severe microcephaly v1.61 RMI1 Louise Daugherty Source NHS GMS was added to RMI1.
Severe microcephaly v1.61 RAD51C Louise Daugherty Source NHS GMS was added to RAD51C.
Severe microcephaly v1.61 QARS Louise Daugherty Source NHS GMS was added to QARS.
Severe microcephaly v1.61 MRE11 Louise Daugherty Source NHS GMS was added to MRE11.
Severe microcephaly v1.61 CRIPT Louise Daugherty Source NHS GMS was added to CRIPT.
Severe microcephaly v1.61 COASY Louise Daugherty Source NHS GMS was added to COASY.
Severe microcephaly v1.61 ZEB2 Louise Daugherty Source NHS GMS was added to ZEB2.
Severe microcephaly v1.61 XRCC4 Louise Daugherty Source NHS GMS was added to XRCC4.
Severe microcephaly v1.61 WDR73 Louise Daugherty Source NHS GMS was added to WDR73.
Severe microcephaly v1.61 WDR62 Louise Daugherty Source NHS GMS was added to WDR62.
Severe microcephaly v1.61 TUBGCP6 Louise Daugherty Source NHS GMS was added to TUBGCP6.
Severe microcephaly v1.61 TUBGCP4 Louise Daugherty Source NHS GMS was added to TUBGCP4.
Severe microcephaly v1.61 TRMT10A Louise Daugherty Source NHS GMS was added to TRMT10A.
Severe microcephaly v1.61 TRAIP Louise Daugherty Source NHS GMS was added to TRAIP.
Severe microcephaly v1.61 TOP3A Louise Daugherty Source NHS GMS was added to TOP3A.
Severe microcephaly v1.61 STIL Louise Daugherty Source NHS GMS was added to STIL.
Severe microcephaly v1.61 STAMBP Louise Daugherty Source NHS GMS was added to STAMBP.
Severe microcephaly v1.61 SMC3 Louise Daugherty Source NHS GMS was added to SMC3.
Severe microcephaly v1.61 SMC1A Louise Daugherty Source NHS GMS was added to SMC1A.
Severe microcephaly v1.61 SLX4 Louise Daugherty Source NHS GMS was added to SLX4.
Severe microcephaly v1.61 SLC9A6 Louise Daugherty Source NHS GMS was added to SLC9A6.
Severe microcephaly v1.61 SLC25A19 Louise Daugherty Source NHS GMS was added to SLC25A19.
Severe microcephaly v1.61 RTTN Louise Daugherty Source NHS GMS was added to RTTN.
Severe microcephaly v1.61 RPL10 Louise Daugherty Source NHS GMS was added to RPL10.
Severe microcephaly v1.61 RNU4ATAC Louise Daugherty Source NHS GMS was added to RNU4ATAC.
Severe microcephaly v1.61 RBBP8 Louise Daugherty Source NHS GMS was added to RBBP8.
Severe microcephaly v1.61 RAD21 Louise Daugherty Source NHS GMS was added to RAD21.
Severe microcephaly v1.61 PQBP1 Louise Daugherty Source NHS GMS was added to PQBP1.
Severe microcephaly v1.61 POC1A Louise Daugherty Source NHS GMS was added to POC1A.
Severe microcephaly v1.61 PNKP Louise Daugherty Source NHS GMS was added to PNKP.
Severe microcephaly v1.61 PLK4 Louise Daugherty Source NHS GMS was added to PLK4.
Severe microcephaly v1.61 PDHA1 Louise Daugherty Source NHS GMS was added to PDHA1.
Severe microcephaly v1.61 PCNT Louise Daugherty Source NHS GMS was added to PCNT.
Severe microcephaly v1.61 PALB2 Louise Daugherty Source NHS GMS was added to PALB2.
Severe microcephaly v1.61 ORC6 Louise Daugherty Source NHS GMS was added to ORC6.
Severe microcephaly v1.61 ORC4 Louise Daugherty Source NHS GMS was added to ORC4.
Severe microcephaly v1.61 ORC1 Louise Daugherty Source NHS GMS was added to ORC1.
Severe microcephaly v1.61 NIPBL Louise Daugherty Source NHS GMS was added to NIPBL.
Severe microcephaly v1.61 NHEJ1 Louise Daugherty Source NHS GMS was added to NHEJ1.
Severe microcephaly v1.61 NDE1 Louise Daugherty Source NHS GMS was added to NDE1.
Severe microcephaly v1.61 NBN Louise Daugherty Source NHS GMS was added to NBN.
Severe microcephaly v1.61 MYCN Louise Daugherty Source NHS GMS was added to MYCN.
Severe microcephaly v1.61 MSMO1 Louise Daugherty Source NHS GMS was added to MSMO1.
Severe microcephaly v1.61 MFSD2A Louise Daugherty Source NHS GMS was added to MFSD2A.
Severe microcephaly v1.61 MCPH1 Louise Daugherty Source NHS GMS was added to MCPH1.
Severe microcephaly v1.61 LIG4 Louise Daugherty Source NHS GMS was added to LIG4.
Severe microcephaly v1.61 LARP7 Louise Daugherty Source NHS GMS was added to LARP7.
Severe microcephaly v1.61 KIF11 Louise Daugherty Source NHS GMS was added to KIF11.
Severe microcephaly v1.61 IGF1R Louise Daugherty Source NHS GMS was added to IGF1R.
Severe microcephaly v1.61 IGF1 Louise Daugherty Source NHS GMS was added to IGF1.
Severe microcephaly v1.61 IER3IP1 Louise Daugherty Source NHS GMS was added to IER3IP1.
Severe microcephaly v1.61 IARS Louise Daugherty Source NHS GMS was added to IARS.
Severe microcephaly v1.61 HDAC8 Louise Daugherty Source NHS GMS was added to HDAC8.
Severe microcephaly v1.61 GMNN Louise Daugherty Source NHS GMS was added to GMNN.
Severe microcephaly v1.61 FANCL Louise Daugherty Source NHS GMS was added to FANCL.
Severe microcephaly v1.61 FANCI Louise Daugherty Source NHS GMS was added to FANCI.
Severe microcephaly v1.61 FANCG Louise Daugherty Source NHS GMS was added to FANCG.
Severe microcephaly v1.61 FANCF Louise Daugherty Source NHS GMS was added to FANCF.
Severe microcephaly v1.61 FANCE Louise Daugherty Source NHS GMS was added to FANCE.
Severe microcephaly v1.61 FANCD2 Louise Daugherty Source NHS GMS was added to FANCD2.
Severe microcephaly v1.61 FANCC Louise Daugherty Source NHS GMS was added to FANCC.
Severe microcephaly v1.61 FANCB Louise Daugherty Source NHS GMS was added to FANCB.
Severe microcephaly v1.61 FANCA Louise Daugherty Source NHS GMS was added to FANCA.
Severe microcephaly v1.61 ERCC8 Louise Daugherty Source NHS GMS was added to ERCC8.
Severe microcephaly v1.61 ERCC6 Louise Daugherty Source NHS GMS was added to ERCC6.
Severe microcephaly v1.61 ERCC4 Louise Daugherty Source NHS GMS was added to ERCC4.
Severe microcephaly v1.61 EFTUD2 Louise Daugherty Source NHS GMS was added to EFTUD2.
Severe microcephaly v1.61 DYRK1A Louise Daugherty Source NHS GMS was added to DYRK1A.
Severe microcephaly v1.61 DPP6 Louise Daugherty Source NHS GMS was added to DPP6.
Severe microcephaly v1.61 DONSON Louise Daugherty Source NHS GMS was added to DONSON.
Severe microcephaly v1.61 DIAPH1 Louise Daugherty Source NHS GMS was added to DIAPH1.
Severe microcephaly v1.61 DHCR7 Louise Daugherty Source NHS GMS was added to DHCR7.
Severe microcephaly v1.61 DDX11 Louise Daugherty Source NHS GMS was added to DDX11.
Severe microcephaly v1.61 CTNNB1 Louise Daugherty Source NHS GMS was added to CTNNB1.
Severe microcephaly v1.61 CREBBP Louise Daugherty Source NHS GMS was added to CREBBP.
Severe microcephaly v1.61 CKAP2L Louise Daugherty Source NHS GMS was added to CKAP2L.
Severe microcephaly v1.61 CIT Louise Daugherty Source NHS GMS was added to CIT.
Severe microcephaly v1.61 CEP63 Louise Daugherty Source NHS GMS was added to CEP63.
Severe microcephaly v1.61 CEP152 Louise Daugherty Source NHS GMS was added to CEP152.
Severe microcephaly v1.61 CEP135 Louise Daugherty Source NHS GMS was added to CEP135.
Severe microcephaly v1.61 CENPJ Louise Daugherty Source NHS GMS was added to CENPJ.
Severe microcephaly v1.61 CENPF Louise Daugherty Source NHS GMS was added to CENPF.
Severe microcephaly v1.61 CDT1 Louise Daugherty Source NHS GMS was added to CDT1.
Severe microcephaly v1.61 CDK5RAP2 Louise Daugherty Source NHS GMS was added to CDK5RAP2.
Severe microcephaly v1.61 CASK Louise Daugherty Source NHS GMS was added to CASK.
Severe microcephaly v1.61 BRIP1 Louise Daugherty Source NHS GMS was added to BRIP1.
Severe microcephaly v1.61 BRCA2 Louise Daugherty Source NHS GMS was added to BRCA2.
Severe microcephaly v1.61 BLM Louise Daugherty Source NHS GMS was added to BLM.
Severe microcephaly v1.61 ATRX Louise Daugherty Source NHS GMS was added to ATRX.
Severe microcephaly v1.61 ATR Louise Daugherty Source NHS GMS was added to ATR.
Severe microcephaly v1.61 ASPM Louise Daugherty Source NHS GMS was added to ASPM.
Severe microcephaly v1.61 PRUNE1 Louise Daugherty Source NHS GMS was added to PRUNE1.
Severe microcephaly v1.61 KNL1 Louise Daugherty Source NHS GMS was added to KNL1.
Severe microcephaly v1.61 KIF1BP Louise Daugherty Source NHS GMS was added to KIF1BP.
Severe microcephaly v1.60 UFC1 Louise Daugherty changed review comment from: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene recommended to be added to the panel by Astrid Weber during the call (Geoff Woods is one of the authors). it was suggested that Geoff Woods opinion on this gene would be helpful too, in view of the presence on his publication of the UFM1 gene. PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green
Sources: Expert list; to: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene recommended to be added to the panel by Astrid Weber during the call (Geoff Woods is one of the authors). It was suggested that Geoff Woods opinion on this gene would be helpful too, in view of the presence on his publication of the UFM1 gene. PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green
Sources: Expert list
Severe microcephaly v1.60 UFC1 Louise Daugherty edited their review of gene: UFC1: Changed rating: GREEN
Severe microcephaly v1.60 UFC1 Louise Daugherty gene: UFC1 was added
gene: UFC1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth, 618076; microcephaly
Review for gene: UFC1 was set to AMBER
Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene recommended to be added to the panel by Astrid Weber during the call (Geoff Woods is one of the authors). it was suggested that Geoff Woods opinion on this gene would be helpful too, in view of the presence on his publication of the UFM1 gene. PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green
Sources: Expert list
Severe microcephaly v1.59 ZNHIT3 Louise Daugherty gene: ZNHIT3 was added
gene: ZNHIT3 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: ZNHIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNHIT3 were set to PEHO syndrome, 260565; microcephaly
Review for gene: ZNHIT3 was set to GREEN
Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green
Sources: Expert list
Severe microcephaly v1.58 UBA5 Louise Daugherty changed review comment from: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green.
Sources: Expert list; to: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green.
Sources: Expert list
Severe microcephaly v1.58 PCLO Louise Daugherty gene: PCLO was added
gene: PCLO was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia, type 3, 608027
Review for gene: PCLO was set to GREEN
Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green
Sources: Expert list
Severe microcephaly v1.57 UFM1 Louise Daugherty Classified gene: UFM1 as Green List (high evidence)
Severe microcephaly v1.57 UFM1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and PMIDs as recommended during the call and in light of evidence as evidence to gene can be upgraded to Green
Severe microcephaly v1.57 UFM1 Louise Daugherty Gene: ufm1 has been classified as Green List (High Evidence).
Severe microcephaly v1.56 UFM1 Louise Daugherty Added comment: Comment on publications: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019 : added PMIDs as recommended to support rating of gene to be Green
Severe microcephaly v1.56 UFM1 Louise Daugherty Publications for gene: UFM1 were set to
Severe microcephaly v1.55 CCDC88A Louise Daugherty Phenotypes for gene: CCDC88A were changed from PEHO syndrome-like, 617507 to PEHO syndrome-like, 617507; microcephaly
Severe microcephaly v1.54 UFM1 Louise Daugherty Phenotypes for gene: UFM1 were changed from Leukodystrophy, hypomyelinating, 14, 617899 to Leukodystrophy, hypomyelinating, 14, 617899; microcephaly
Severe microcephaly v1.53 UFM1 Louise Daugherty gene: UFM1 was added
gene: UFM1 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: UFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UFM1 were set to Leukodystrophy, hypomyelinating, 14, 617899
Review for gene: UFM1 was set to GREEN
Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green.
Sources: Expert list
Severe microcephaly v1.52 UBA5 Louise Daugherty gene: UBA5 was added
gene: UBA5 was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: UBA5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBA5 were set to Epileptic encephalopathy, early infantile, 44, 617132
Review for gene: UBA5 was set to GREEN
Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green.
Sources: Expert list
Severe microcephaly v1.51 CCDC88A Louise Daugherty gene: CCDC88A was added
gene: CCDC88A was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for gene: CCDC88A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CCDC88A were set to PEHO syndrome-like, 617507
Review for gene: CCDC88A was set to GREEN
Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green.
Sources: Expert list
Severe microcephaly v1.50 PALB2 Helen Brittain Classified gene: PALB2 as Amber List (moderate evidence)
Severe microcephaly v1.50 PALB2 Helen Brittain Added comment: Comment on list classification: As per structural neurological working group webex on 11th July 2019
Severe microcephaly v1.50 PALB2 Helen Brittain Gene: palb2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v1.49 PALB2 Helen Brittain reviewed gene: PALB2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v1.48 TRMT1 Rebecca Foulger gene: TRMT1 was added
gene: TRMT1 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: TRMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1 were set to 30289604
Phenotypes for gene: TRMT1 were set to Non‐syndromal congenital microcephaly
Review for gene: TRMT1 was set to RED
Added comment: Added TRMT1 to the microcephaly panel based on PMID:30289604 (Blaesius et al., 2018) who report 4 patients from 2 unrelated consanguineous Pakistani families with homozygous variants in TRMT1 and intellectual disability. Non‐syndromal microcephaly was diagnosed at birth in three of the patients (V:2 from Family 1 (OFC -4.9 SD), and III.3 (OFC -4.1 SD) and III.4 (OFC -4 SD) from Family 2). The authors note that the clinical features are reminiscent of autosomal recessive primary microcephaly (MCPH). Rated as Red awaiting further cases.
Sources: Literature
Severe microcephaly v1.47 ISCA-37501-Loss Louise Daugherty Triplosensitivity Score for ISCA-37501-Loss was changed from 2 to None.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Severe microcephaly v1.46 ISCA-37501-Loss Louise Daugherty Classified Region: ISCA-37501-Loss as Green List (high evidence)
Severe microcephaly v1.46 ISCA-37501-Loss Louise Daugherty Region: isca-37501-loss has been classified as Green List (High Evidence).
Severe microcephaly v1.45 ISCA-37501-Loss Louise Daugherty Region: ISCA-37501-Loss was added
Region: ISCA-37501-Loss was added to Severe microcephaly. Sources: Expert list
Mode of inheritance for Region: ISCA-37501-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37501-Loss were set to 20206336; 22052739
Phenotypes for Region: ISCA-37501-Loss were set to Chromosome 17q23.1-q23.2 deletion syndrome, 613355; PMID:20206336 mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, hand, foot and limb abnormalities; PMID: 22052739 Developmental delay, heart defects, microcephaly, postnatal growth retardation, hand, foot and limb abnormalities, sensorineural hearing loss
Review for Region: ISCA-37501-Loss was set to GREEN
Added comment: Sources: Expert list
Severe microcephaly v1.44 Louise Daugherty List of related panels changed from Primary Microcephaly - Microcephalic Dwarfism Spectrum; Severe microcephaly; GMS R88 to Primary Microcephaly - Microcephalic Dwarfism Spectrum; Severe microcephaly
Severe microcephaly v1.42 COASY Louise Daugherty Publications for gene: COASY were set to 30089828
Severe microcephaly v1.41 COASY Louise Daugherty commented on gene: COASY: added watchlist tag
Severe microcephaly v1.41 COASY Louise Daugherty Tag watchlist tag was added to gene: COASY.
Severe microcephaly v1.41 COASY Louise Daugherty Classified gene: COASY as Amber List (moderate evidence)
Severe microcephaly v1.41 COASY Louise Daugherty Added comment: Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported.
Severe microcephaly v1.41 COASY Louise Daugherty Gene: coasy has been classified as Amber List (Moderate Evidence).
Severe microcephaly v1.40 COASY Louise Daugherty gene: COASY was added
gene: COASY was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828
Phenotypes for gene: COASY were set to Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis
Review for gene: COASY was set to AMBER
Added comment: From Dijk et al. (2018) PMID: 30089828 variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis. A single variant was identified in 4 individuals in 2 unrelated families with PCH, prenatal onset microcephaly, and arthrogryposis. In both families, the variant c.[1549_1550delAG]; [1486-3 C>G] segregated wth the phenotype. No CoA synthase protein was detected in patient cells by immunoblot analysis and CoA synthase activity was virtually absent. Partial CoA synthase defects were previously described by Dusi et al. (2014) PMID: 24360804 as a cause of COASY Protein-Associated Neurodegeneration (CoPAN), a type of Neurodegeneration and Brain Iron Accumulation (MIM: 615643). Dijk et al. (2018) PMID: 30089828 demonstrate that near complete loss of function variants in COASY are associated with lethal PCH and arthrogryposis.
Sources: Literature
Severe microcephaly v1.39 Ellen McDonagh List of related panels changed from Primary Microcephaly - Microcephalic Dwarfism Spectrum to Primary Microcephaly - Microcephalic Dwarfism Spectrum; Severe microcephaly; GMS R88
Severe microcephaly v1.38 Ellen McDonagh Panel name changed from Primary Microcephaly - Microcephalic Dwarfism Spectrum to Severe microcephaly
List of related panels changed from to Primary Microcephaly - Microcephalic Dwarfism Spectrum
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Severe microcephaly v1.37 ISCA-37425-Gain Louise Daugherty Region: ISCA-37425-Gain was added
Region: ISCA-37425-Gain was added to Primary Microcephaly - Microcephalic Dwarfism Spectrum. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37425-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37425-Gain were set to 23913520; 23599694
Phenotypes for Region: ISCA-37425-Gain were set to Microcephaly, short stature and developmental delay; short stature, microcephaly, learning disability or mild to moderate ID, and distinctive facial features comprising periorbital fullness, short palpebral fissures, a long nose with broad or long nasal tip, a smooth philtrum and a thin upper lip vermilion. Behavioral problems, ocular and minor hand anomalies may be associated.
Severe microcephaly v1.37 ISCA-37390-Loss Louise Daugherty Region: ISCA-37390-Loss was added
Region: ISCA-37390-Loss was added to Primary Microcephaly - Microcephalic Dwarfism Spectrum. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37390-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37390-Loss were set to 11238681; 15635506
Phenotypes for Region: ISCA-37390-Loss were set to 123450; PMID 15635506: characteristic cry, speech delay, facial dysmorphology, and level of mental retardation. PMID 11238681: interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731, study supports hypothesis of a separate region in p15.3 for the speech delay
Severe microcephaly v1.37 ISCA-37406-Loss Louise Daugherty Region: ISCA-37406-Loss was added
Region: ISCA-37406-Loss was added to Primary Microcephaly - Microcephalic Dwarfism Spectrum. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37406-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37406-Loss were set to 10573006; 16783566
Phenotypes for Region: ISCA-37406-Loss were set to PMID: 10573006 death in infancy, accessory spleens, hypoplastic left heart, abnormal pulmonary lobulation, renal agenesis (patient 1), severe neonatal seizures (patient 2). PMID 16783566: failure to thrive, life-threatening malformations, and/or critical infections, and all died in infancy (5 weeks, 7 months, and 9 months, respectivelyFrom Genetics Home Reference: short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes; 610543
Severe microcephaly v1.37 ISCA-37408-Loss Louise Daugherty Region: ISCA-37408-Loss was added
Region: ISCA-37408-Loss was added to Primary Microcephaly - Microcephalic Dwarfism Spectrum. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37408-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37408-Loss were set to 16963482; 22579565; 18245392
Phenotypes for Region: ISCA-37408-Loss were set to PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more); 612513; PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect
Severe microcephaly RMI1 Sarah Leigh classified RMI1 as Amber List (moderate evidence)
Severe microcephaly RMI1 Sarah Leigh Added gene to panel
Severe microcephaly TOP3A Sarah Leigh classified TOP3A as Green List (high evidence)
Severe microcephaly TOP3A Sarah Leigh Added gene to panel
Severe microcephaly WDR4 Louise Daugherty classified WDR4 as Amber List (moderate evidence)
Severe microcephaly WDR4 Ellen McDonagh edited their review of WDR4
Severe microcephaly MRE11 Louise Daugherty classified MRE11 as Amber List (moderate evidence)
Severe microcephaly MRE11 Louise Daugherty edited their review of MRE11
Severe microcephaly MRE11 Louise Daugherty Added gene to panel
Severe microcephaly IARS Louise Daugherty classified IARS as Green List (high evidence)
Severe microcephaly IARS Louise Daugherty edited their review of IARS
Severe microcephaly IARS Louise Daugherty Added gene to panel
Severe microcephaly EOMES Ellen McDonagh commented on EOMES
Severe microcephaly EOMES Ellen McDonagh Added gene to panel
Severe microcephaly FANCM Ellen McDonagh reviewed FANCM
Severe microcephaly RPL10 Sarah Leigh classified RPL10 as green
Severe microcephaly RPL10 Sarah Leigh commented on RPL10
Severe microcephaly RPL10 Sarah Leigh added RPL10 to panel
Severe microcephaly RPL10 Sarah Leigh reviewed RPL10
Severe microcephaly DONSON Sarah Leigh classified DONSON as green
Severe microcephaly DONSON Sarah Leigh reviewed DONSON
Severe microcephaly PLAA Rebecca Foulger classified PLAA as red
Severe microcephaly PLAA Rebecca Foulger commented on PLAA
Severe microcephaly PLAA Rebecca Foulger commented on PLAA
Severe microcephaly PLAA Rebecca Foulger added PLAA to panel
Severe microcephaly PLAA Rebecca Foulger reviewed PLAA
Severe microcephaly TAF13 Ellen McDonagh classified TAF13 as amber
Severe microcephaly TAF13 Ellen McDonagh added TAF13 to panel
Severe microcephaly TAF13 Ellen McDonagh reviewed TAF13
Severe microcephaly WDFY3 Rebecca Foulger classified WDFY3 as red
Severe microcephaly WDFY3 Rebecca Foulger added WDFY3 to panel
Severe microcephaly WDFY3 Rebecca Foulger reviewed WDFY3
Severe microcephaly DONSON Olivia Niblock added DONSON to panel
Severe microcephaly DONSON Olivia Niblock reviewed DONSON
Severe microcephaly PRUNE Ellen McDonagh reviewed PRUNE
Severe microcephaly RAD51C Rebecca Foulger edited their review of RAD51C
Severe microcephaly RAD51C Rebecca Foulger classified RAD51C as amber
Severe microcephaly RAD51C Rebecca Foulger commented on RAD51C
Severe microcephaly MSMO1 Sarah Leigh classified MSMO1 as green
Severe microcephaly MSMO1 Sarah Leigh commented on MSMO1
Severe microcephaly PRUNE Rebecca Foulger commented on PRUNE
Severe microcephaly PDHA1 emma baple edited their review of PDHA1
Severe microcephaly PDHA1 emma baple marked PDHA1 as ready
Severe microcephaly PDHA1 emma baple classified PDHA1 as green
Severe microcephaly PDHA1 emma baple added PDHA1 to panel
Severe microcephaly PDHA1 emma baple reviewed PDHA1
Severe microcephaly PRUNE emma baple marked PRUNE as ready
Severe microcephaly PRUNE emma baple classified PRUNE as green
Severe microcephaly PRUNE emma baple added PRUNE to panel
Severe microcephaly PRUNE emma baple reviewed PRUNE
Severe microcephaly Rebecca Foulger promoted panel to version 1
Severe microcephaly DIAPH1 Rebecca Foulger classified DIAPH1 as green
Severe microcephaly SMC1A Rebecca Foulger classified SMC1A as green
Severe microcephaly SMC1A Rebecca Foulger commented on SMC1A
Severe microcephaly SMC1A Rebecca Foulger edited their review of SMC1A
Severe microcephaly DPP6 Rebecca Foulger classified DPP6 as green
Severe microcephaly HDAC8 Rebecca Foulger classified HDAC8 as green
Severe microcephaly HDAC8 Rebecca Foulger commented on HDAC8
Severe microcephaly HDAC8 Rebecca Foulger commented on HDAC8
Severe microcephaly NIPBL Rebecca Foulger classified NIPBL as green
Severe microcephaly NIPBL Rebecca Foulger commented on NIPBL
Severe microcephaly SMC1A Rebecca Foulger commented on SMC1A
Severe microcephaly SMC3 Rebecca Foulger classified SMC3 as green
Severe microcephaly SMC3 Rebecca Foulger commented on SMC3
Severe microcephaly RAD21 Rebecca Foulger classified RAD21 as green
Severe microcephaly RAD21 Rebecca Foulger commented on RAD21
Severe microcephaly RAD21 Rebecca Foulger commented on RAD21
Severe microcephaly RAD21 Rebecca Foulger commented on RAD21
Severe microcephaly DPP6 Rebecca Foulger commented on DPP6
Severe microcephaly POC1A Rebecca Foulger classified POC1A as green
Severe microcephaly DYRK1A Rebecca Foulger commented on DYRK1A
Severe microcephaly DYRK1A Rebecca Foulger classified DYRK1A as green
Severe microcephaly DYRK1A Rebecca Foulger commented on DYRK1A
Severe microcephaly DYRK1A Rebecca Foulger commented on DYRK1A
Severe microcephaly CTNNB1 Rebecca Foulger classified CTNNB1 as green
Severe microcephaly CTNNB1 Rebecca Foulger commented on CTNNB1
Severe microcephaly RBBP8 Rebecca Foulger classified RBBP8 as green
Severe microcephaly ZNF335 Rebecca Foulger classified ZNF335 as amber
Severe microcephaly ZNF335 Rebecca Foulger commented on ZNF335
Severe microcephaly ZNF335 Rebecca Foulger commented on ZNF335
Severe microcephaly ZNF335 Rebecca Foulger commented on ZNF335
Severe microcephaly WDR4 Rebecca Foulger commented on WDR4
Severe microcephaly TRMT10A Rebecca Foulger classified TRMT10A as green
Severe microcephaly TRMT10A Rebecca Foulger commented on TRMT10A
Severe microcephaly TRMT10A Rebecca Foulger commented on TRMT10A
Severe microcephaly TRMT10A Rebecca Foulger commented on TRMT10A
Severe microcephaly TRMT10A Rebecca Foulger commented on TRMT10A
Severe microcephaly RBBP8 Rebecca Foulger commented on RBBP8
Severe microcephaly RBBP8 Rebecca Foulger commented on RBBP8
Severe microcephaly RBBP8 Rebecca Foulger commented on RBBP8
Severe microcephaly RBBP8 Rebecca Foulger commented on RBBP8
Severe microcephaly POC1A Rebecca Foulger commented on POC1A
Severe microcephaly POC1A Rebecca Foulger commented on POC1A
Severe microcephaly POC1A Rebecca Foulger commented on POC1A
Severe microcephaly POC1A Rebecca Foulger commented on POC1A
Severe microcephaly POC1A Rebecca Foulger commented on POC1A
Severe microcephaly PHC1 Rebecca Foulger commented on PHC1
Severe microcephaly PHC1 Rebecca Foulger commented on PHC1
Severe microcephaly NSMCE2 Rebecca Foulger commented on NSMCE2
Severe microcephaly DPP6 Rebecca Foulger commented on DPP6
Severe microcephaly DDX11 Rebecca Foulger classified DDX11 as green
Severe microcephaly DDX11 Rebecca Foulger commented on DDX11
Severe microcephaly CDC6 Rebecca Foulger commented on CDC6
Severe microcephaly TUBGCP3 Rebecca Foulger commented on TUBGCP3
Severe microcephaly NSMCE2 Rebecca Foulger commented on NSMCE2
Severe microcephaly ERCC5 Rebecca Foulger classified ERCC5 as red
Severe microcephaly ERCC5 Rebecca Foulger commented on ERCC5
Severe microcephaly ERCC5 Rebecca Foulger commented on ERCC5
Severe microcephaly ERCC5 Rebecca Foulger added ERCC5 to panel
Severe microcephaly ERCC5 Rebecca Foulger reviewed ERCC5
Severe microcephaly ERCC4 Rebecca Foulger classified ERCC4 as green
Severe microcephaly ERCC4 Rebecca Foulger commented on ERCC4
Severe microcephaly ERCC4 Rebecca Foulger commented on ERCC4
Severe microcephaly ERCC4 Rebecca Foulger added ERCC4 to panel
Severe microcephaly ERCC4 Rebecca Foulger reviewed ERCC4
Severe microcephaly FANCM Rebecca Foulger classified FANCM as red
Severe microcephaly FANCM Rebecca Foulger commented on FANCM
Severe microcephaly WDR73 Rebecca Foulger classified WDR73 as green
Severe microcephaly CRIPT Rebecca Foulger classified CRIPT as amber
Severe microcephaly CRIPT Rebecca Foulger commented on CRIPT
Severe microcephaly KIAA1279 Rebecca Foulger classified KIAA1279 as green
Severe microcephaly KIAA1279 Rebecca Foulger commented on KIAA1279
Severe microcephaly LARP7 Rebecca Foulger classified LARP7 as green
Severe microcephaly LARP7 Rebecca Foulger edited their review of LARP7
Severe microcephaly LARP7 Rebecca Foulger commented on LARP7
Severe microcephaly ATRX Rebecca Foulger edited their review of ATRX
Severe microcephaly ATRX Rebecca Foulger classified ATRX as green
Severe microcephaly ATRX Rebecca Foulger commented on ATRX
Severe microcephaly CREBBP Rebecca Foulger marked CREBBP as ready
Severe microcephaly MYCN Rebecca Foulger marked MYCN as ready
Severe microcephaly MYCN Rebecca Foulger classified MYCN as green
Severe microcephaly MYCN Rebecca Foulger commented on MYCN
Severe microcephaly CREBBP Rebecca Foulger classified CREBBP as green
Severe microcephaly CREBBP Rebecca Foulger commented on CREBBP
Severe microcephaly MYCN emma baple reviewed MYCN
Severe microcephaly KIAA1279 emma baple reviewed KIAA1279
Severe microcephaly CREBBP emma baple reviewed CREBBP
Severe microcephaly ATRX emma baple reviewed ATRX
Severe microcephaly SLX4 emma baple reviewed SLX4
Severe microcephaly RAD51C emma baple reviewed RAD51C
Severe microcephaly PALB2 emma baple reviewed PALB2
Severe microcephaly FANCL emma baple reviewed FANCL
Severe microcephaly FANCI emma baple reviewed FANCI
Severe microcephaly FANCG emma baple reviewed FANCG
Severe microcephaly FANCF emma baple reviewed FANCF
Severe microcephaly FANCE emma baple reviewed FANCE
Severe microcephaly FANCD2 emma baple reviewed FANCD2
Severe microcephaly FANCC emma baple reviewed FANCC
Severe microcephaly FANCB emma baple reviewed FANCB
Severe microcephaly FANCA emma baple reviewed FANCA
Severe microcephaly ERCC8 emma baple reviewed ERCC8
Severe microcephaly ERCC6 emma baple reviewed ERCC6
Severe microcephaly BRIP1 emma baple reviewed BRIP1
Severe microcephaly BRCA2 emma baple reviewed BRCA2
Severe microcephaly KIAA1279 Rebecca Foulger commented on KIAA1279
Severe microcephaly PNKP Rebecca Foulger classified PNKP as green
Severe microcephaly PNKP Rebecca Foulger commented on PNKP
Severe microcephaly WDR73 Rebecca Foulger commented on WDR73
Severe microcephaly SLC9A6 Rebecca Foulger classified SLC9A6 as green
Severe microcephaly SLC9A6 Rebecca Foulger commented on SLC9A6
Severe microcephaly IER3IP1 Rebecca Foulger classified IER3IP1 as green
Severe microcephaly IER3IP1 Rebecca Foulger commented on IER3IP1
Severe microcephaly TRMT10A Rebecca Foulger commented on TRMT10A
Severe microcephaly PPP1R15B Rebecca Foulger commented on PPP1R15B
Severe microcephaly MSMO1 Rebecca Foulger classified MSMO1 as red
Severe microcephaly MSMO1 Rebecca Foulger commented on MSMO1
Severe microcephaly POC1A Rebecca Foulger classified POC1A as red
Severe microcephaly CRIPT Rebecca Foulger classified CRIPT as amber
Severe microcephaly CRIPT Rebecca Foulger added CRIPT to panel
Severe microcephaly CRIPT Rebecca Foulger reviewed CRIPT
Severe microcephaly QARS Rebecca Foulger classified QARS as amber
Severe microcephaly QARS Rebecca Foulger commented on QARS
Severe microcephaly DIAPH1 Rebecca Foulger classified DIAPH1 as amber
Severe microcephaly DIAPH1 Rebecca Foulger commented on DIAPH1
Severe microcephaly QARS Alice Gardham added QARS to panel
Severe microcephaly QARS Alice Gardham reviewed QARS
Severe microcephaly CKAP2L Alice Gardham marked CKAP2L as ready
Severe microcephaly CKAP2L Alice Gardham classified CKAP2L as green
Severe microcephaly CKAP2L Alice Gardham commented on CKAP2L
Severe microcephaly STAMBP Alice Gardham marked STAMBP as ready
Severe microcephaly STAMBP Alice Gardham classified STAMBP as green
Severe microcephaly STAMBP Alice Gardham added STAMBP to panel
Severe microcephaly STAMBP Alice Gardham reviewed STAMBP
Severe microcephaly NHEJ1 Alice Gardham marked NHEJ1 as ready
Severe microcephaly NHEJ1 Alice Gardham added NHEJ1 to panel
Severe microcephaly NHEJ1 Alice Gardham reviewed NHEJ1
Severe microcephaly DDX11 Alice Gardham added DDX11 to panel
Severe microcephaly DDX11 Alice Gardham reviewed DDX11
Severe microcephaly NBN Alice Gardham marked NBN as ready
Severe microcephaly NBN Alice Gardham added NBN to panel
Severe microcephaly NBN Alice Gardham reviewed NBN
Severe microcephaly ZEB2 Alice Gardham marked ZEB2 as ready
Severe microcephaly ZEB2 Alice Gardham added ZEB2 to panel
Severe microcephaly ZEB2 Alice Gardham reviewed ZEB2
Severe microcephaly DHCR7 Alice Gardham marked DHCR7 as ready
Severe microcephaly DHCR7 Alice Gardham added DHCR7 to panel
Severe microcephaly DHCR7 Alice Gardham reviewed DHCR7
Severe microcephaly CIT Alice Gardham marked CIT as ready
Severe microcephaly CIT Alice Gardham classified CIT as green
Severe microcephaly CIT Alice Gardham reviewed CIT
Severe microcephaly ANKLE2 Alice Gardham marked ANKLE2 as ready
Severe microcephaly ANKLE2 Alice Gardham reviewed ANKLE2
Severe microcephaly MFSD2A Alice Gardham marked MFSD2A as ready
Severe microcephaly MFSD2A Alice Gardham classified MFSD2A as green
Severe microcephaly MFSD2A Alice Gardham reviewed MFSD2A
Severe microcephaly ZNF335 Alice Gardham reviewed ZNF335
Severe microcephaly MCPH1 Alice Gardham marked MCPH1 as ready
Severe microcephaly MCPH1 Alice Gardham commented on MCPH1
Severe microcephaly CDK5RAP2 Alice Gardham marked CDK5RAP2 as ready
Severe microcephaly CDK5RAP2 Alice Gardham commented on CDK5RAP2
Severe microcephaly CASK Alice Gardham marked CASK as ready
Severe microcephaly ASPM Alice Gardham marked ASPM as ready
Severe microcephaly PCNT Alice Gardham marked PCNT as ready
Severe microcephaly PCNT Alice Gardham commented on PCNT
Severe microcephaly RTTN Alice Gardham marked RTTN as ready
Severe microcephaly RTTN Alice Gardham classified RTTN as green
Severe microcephaly RTTN Alice Gardham reviewed RTTN
Severe microcephaly CASC5 Alice Gardham marked CASC5 as ready
Severe microcephaly CASC5 Alice Gardham reviewed CASC5
Severe microcephaly STIL Alice Gardham marked STIL as ready
Severe microcephaly STIL Alice Gardham commented on STIL
Severe microcephaly WDR62 Alice Gardham marked WDR62 as ready
Severe microcephaly WDR62 Alice Gardham commented on WDR62
Severe microcephaly CEP152 Alice Gardham marked CEP152 as ready
Severe microcephaly CEP152 Alice Gardham commented on CEP152
Severe microcephaly CENPJ Alice Gardham marked CENPJ as ready
Severe microcephaly CENPJ Alice Gardham marked CENPJ as ready
Severe microcephaly CENPJ Alice Gardham commented on CENPJ
Severe microcephaly NDE1 Alice Gardham marked NDE1 as ready
Severe microcephaly NDE1 Alice Gardham classified NDE1 as green
Severe microcephaly NDE1 Alice Gardham reviewed NDE1
Severe microcephaly BLM Alice Gardham marked BLM as ready
Severe microcephaly BLM Alice Gardham reviewed BLM
Severe microcephaly LIG4 Alice Gardham marked LIG4 as ready
Severe microcephaly LIG4 Alice Gardham classified LIG4 as green
Severe microcephaly LIG4 Alice Gardham reviewed LIG4
Severe microcephaly XRCC4 Alice Gardham marked XRCC4 as ready
Severe microcephaly XRCC4 Alice Gardham classified XRCC4 as green
Severe microcephaly XRCC4 Alice Gardham reviewed XRCC4
Severe microcephaly CENPF Alice Gardham marked CENPF as ready
Severe microcephaly CENPF Alice Gardham classified CENPF as green
Severe microcephaly CENPF Alice Gardham reviewed CENPF
Severe microcephaly TRAIP Alice Gardham marked TRAIP as ready
Severe microcephaly TRAIP Alice Gardham classified TRAIP as green
Severe microcephaly TRAIP Alice Gardham reviewed TRAIP
Severe microcephaly TUBGCP4 Alice Gardham marked TUBGCP4 as ready
Severe microcephaly TUBGCP4 Alice Gardham marked TUBGCP4 as ready
Severe microcephaly TUBGCP4 Alice Gardham classified TUBGCP4 as green
Severe microcephaly TUBGCP4 Alice Gardham reviewed TUBGCP4
Severe microcephaly PLK4 Alice Gardham marked PLK4 as ready
Severe microcephaly PLK4 Alice Gardham classified PLK4 as green
Severe microcephaly PLK4 Alice Gardham reviewed PLK4
Severe microcephaly TUBGCP6 Alice Gardham marked TUBGCP6 as ready
Severe microcephaly TUBGCP6 Alice Gardham classified TUBGCP6 as green
Severe microcephaly TUBGCP6 Alice Gardham reviewed TUBGCP6
Severe microcephaly PQBP1 Alice Gardham marked PQBP1 as ready
Severe microcephaly PQBP1 Alice Gardham added PQBP1 to panel
Severe microcephaly PQBP1 Alice Gardham reviewed PQBP1
Severe microcephaly RNU4ATAC Alice Gardham marked RNU4ATAC as ready
Severe microcephaly RNU4ATAC Alice Gardham classified RNU4ATAC as green
Severe microcephaly RNU4ATAC Alice Gardham reviewed RNU4ATAC
Severe microcephaly EFTUD2 Alice Gardham marked EFTUD2 as ready
Severe microcephaly EFTUD2 Alice Gardham classified EFTUD2 as green
Severe microcephaly EFTUD2 Alice Gardham added EFTUD2 to panel
Severe microcephaly EFTUD2 Alice Gardham reviewed EFTUD2
Severe microcephaly IGF1R Alice Gardham marked IGF1R as ready
Severe microcephaly IGF1R Alice Gardham reviewed IGF1R
Severe microcephaly IGF1 Alice Gardham marked IGF1 as ready
Severe microcephaly IGF1 Alice Gardham reviewed IGF1
Severe microcephaly KIF11 Alice Gardham marked KIF11 as ready
Severe microcephaly KIF11 Alice Gardham classified KIF11 as green
Severe microcephaly KIF11 Alice Gardham commented on KIF11
Severe microcephaly GMNN Alice Gardham marked GMNN as ready
Severe microcephaly GMNN Alice Gardham classified GMNN as green
Severe microcephaly GMNN Alice Gardham reviewed GMNN
Severe microcephaly CDC6 Alice Gardham reviewed CDC6
Severe microcephaly CDT1 Alice Gardham marked CDT1 as ready
Severe microcephaly CDT1 Alice Gardham classified CDT1 as green
Severe microcephaly CDT1 Alice Gardham reviewed CDT1
Severe microcephaly ORC6 Alice Gardham marked ORC6 as ready
Severe microcephaly ORC6 Alice Gardham classified ORC6 as green
Severe microcephaly ORC6 Alice Gardham reviewed ORC6
Severe microcephaly ORC4 Alice Gardham marked ORC4 as ready
Severe microcephaly ORC4 Alice Gardham classified ORC4 as green
Severe microcephaly ORC4 Alice Gardham reviewed ORC4
Severe microcephaly ORC1 Alice Gardham marked ORC1 as ready
Severe microcephaly ORC1 Alice Gardham classified ORC1 as green
Severe microcephaly ORC1 Alice Gardham classified ORC1 as green
Severe microcephaly ORC1 Alice Gardham reviewed ORC1
Severe microcephaly CEP63 Alice Gardham classified CEP63 as green
Severe microcephaly CEP63 Alice Gardham reviewed CEP63
Severe microcephaly RBBP8 Alice Gardham reviewed RBBP8
Severe microcephaly ATRIP Alice Gardham marked ATRIP as ready
Severe microcephaly ATR Alice Gardham marked ATR as ready
Severe microcephaly ATR Alice Gardham classified ATR as green
Severe microcephaly ATR Alice Gardham reviewed ATR
Severe microcephaly CEP135 Alice Gardham marked CEP135 as ready
Severe microcephaly CEP135 Alice Gardham classified CEP135 as green
Severe microcephaly CEP135 Alice Gardham classified CEP135 as amber
Severe microcephaly CEP135 Alice Gardham reviewed CEP135
Severe microcephaly RNU4ATAC Ellen McDonagh commented on RNU4ATAC
Severe microcephaly DNA2 Rebecca Foulger marked DNA2 as ready
Severe microcephaly DNA2 Rebecca Foulger commented on DNA2
Severe microcephaly DNA2 Rebecca Foulger commented on DNA2
Severe microcephaly NIN Rebecca Foulger marked NIN as ready
Severe microcephaly NIN Rebecca Foulger commented on NIN
Severe microcephaly SLC25A19 Rebecca Foulger commented on SLC25A19
Severe microcephaly CKAP2L Rebecca Foulger commented on CKAP2L
Severe microcephaly KIF11 Rebecca Foulger commented on KIF11
Severe microcephaly CASK Rebecca Foulger commented on CASK
Severe microcephaly PHC1 Rebecca Foulger commented on PHC1
Severe microcephaly DPP6 Rebecca Foulger commented on DPP6
Severe microcephaly WDR4 Rebecca Foulger commented on WDR4
Severe microcephaly CASC5 Rebecca Foulger commented on CASC5
Severe microcephaly CENPE Rebecca Foulger commented on CENPE
Severe microcephaly SASS6 Rebecca Foulger commented on SASS6
Severe microcephaly POC1A Rebecca Foulger commented on POC1A
Severe microcephaly NDE1 Rebecca Foulger commented on NDE1
Severe microcephaly CIT Rebecca Foulger commented on CIT
Severe microcephaly CDK6 Rebecca Foulger commented on CDK6
Severe microcephaly ATRIP Rebecca Foulger commented on ATRIP
Severe microcephaly ASPM Rebecca Foulger commented on ASPM
Severe microcephaly ASPM Rebecca Foulger commented on ASPM
Severe microcephaly AGMO Rebecca Foulger commented on AGMO
Severe microcephaly LARP7 Richard Scott added LARP7 to panel
Severe microcephaly LARP7 Richard Scott reviewed LARP7