ClinVar Miner

Submissions for variant NM_001034116.2(EIF2B4):c.1505C>T (p.Thr502Met)

gnomAD frequency: 0.00001  dbSNP: rs749942048
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778612 SCV000914922 uncertain significance Vanishing white matter disease 2018-10-25 criteria provided, single submitter clinical testing The EIF2B4 c.1502C>T (p.Thr501Met) variant is a missense variant that has been reported in single study and is found in one individual with leukoencephalopathy with vanishing white matter in a compound heterozygous state with a missense variant (Zhang et al. 2015). The p.Thr501Met variant is inherited from the unaffected father. The p.Thr501Met variant is absent from 100 controls and is found at a frequency of 0.000027 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence, the p.Thr501Met variant is classified as a variant of unknown significance but suspicious for pathogenicity for childhood ataxia with central nervous system hypomyelination/vanishing white matter. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx RCV004588240 SCV005080570 likely pathogenic not provided 2023-10-20 criteria provided, single submitter clinical testing Reported using alternate nomenclature (c.1565C>T, p.T522M) with a variant on the opposite allele (in trans) in a patient with vanishing white matter disease in published literature (PMID: 25761052); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34745209, 25761052)

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