ClinVar Miner

Submissions for variant NM_001083961.2(WDR62):c.1576G>A (p.Glu526Lys)

gnomAD frequency: 0.00022  dbSNP: rs147875659
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000000058 SCV000195410 uncertain significance Microcephaly 2, primary, autosomal recessive, with or without cortical malformations 2014-05-19 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000489330 SCV000225557 uncertain significance not provided 2015-01-21 criteria provided, single submitter clinical testing
GeneDx RCV000489330 SCV000576907 uncertain significance not provided 2022-08-30 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28756000, 20729831, 31130284, 31980526, 31258591, 21961505, 25303973, 24228726, 23065275, 34426522)
Illumina Laboratory Services,Illumina RCV000000058 SCV000914841 uncertain significance Microcephaly 2, primary, autosomal recessive, with or without cortical malformations 2018-10-17 criteria provided, single submitter clinical testing The WDR62 c.1576G>A (p.Glu526Lys) variant is a missense variant has been reported in one study, in which it is found in a homozygous state in one individual born to consanguineous Turkish parents, affected with microcephaly, intellectual disability, prognathism, dysconjugate gaze, and dysarthria (Bilg├╝var et al. 2010). The p.Glu526Lys variant was present in 3 of 1290 unrelated Turkish control chromosomes, absent from 1500 Caucasian control chromosomes, and is reported at a frequency of 0.000415 in the Other population of the Genome Aggregation Database. Based on the limited evidence, the p.Glu526Lys variant is classified as a variant of unknown significance but suspicious for pathogenicity for primary microcephaly 2 with or without cortical malformations. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174806 SCV001338152 likely pathogenic Autosomal recessive primary microcephaly 2020-02-11 criteria provided, single submitter clinical testing Variant summary: WDR62 c.1576G>A (p.Glu526Lys) results in a conservative amino acid change located in the WD40-repeat-containing domain (IPR017986) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 253782 control chromosomes (gnomAD and literature). c.1576G>A has been reported in the literature as a homozygous variant in at least one individual from a consanguineous family who was affected with microcephaly and severe mental retardation (Bilguvar_2010). In addition, one clinical diagnostic laboratory cites the variant as being found in an internal sample as a homozygous mutation in an individual affected by central nervous system anomalies in a submission to ClinVar. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. They have cited the variant as uncertain significance (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV000000058 SCV001523667 uncertain significance Microcephaly 2, primary, autosomal recessive, with or without cortical malformations 2020-06-03 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories,Mayo Clinic RCV000489330 SCV001712987 uncertain significance not provided 2019-05-20 criteria provided, single submitter clinical testing
OMIM RCV000000058 SCV000020201 pathogenic Microcephaly 2, primary, autosomal recessive, with or without cortical malformations 2010-09-09 no assertion criteria provided literature only

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