rs61744321
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001083961.2(WDR62):c.2281C>T(p.His761Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00306 in 1,614,130 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 76 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 50 hom. )
Consequence
WDR62
NM_001083961.2 missense
NM_001083961.2 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 3.87
Genes affected
WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00273332).
BP6
?
Variant 19-36092759-C-T is Benign according to our data. Variant chr19-36092759-C-T is described in ClinVar as [Benign]. Clinvar id is 137908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36092759-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR62 | NM_001083961.2 | c.2281C>T | p.His761Tyr | missense_variant | 19/32 | ENST00000401500.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR62 | ENST00000401500.7 | c.2281C>T | p.His761Tyr | missense_variant | 19/32 | 1 | NM_001083961.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0162 AC: 2468AN: 152176Hom.: 76 Cov.: 33
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GnomAD3 exomes AF: 0.00436 AC: 1096AN: 251386Hom.: 25 AF XY: 0.00308 AC XY: 418AN XY: 135882
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GnomAD4 exome AF: 0.00169 AC: 2472AN: 1461836Hom.: 50 Cov.: 32 AF XY: 0.00145 AC XY: 1051AN XY: 727216
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GnomAD4 genome ? AF: 0.0162 AC: 2470AN: 152294Hom.: 76 Cov.: 33 AF XY: 0.0150 AC XY: 1119AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 01, 2013 | - - |
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 24, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
WDR62-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 28, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at