ClinVar Miner

Submissions for variant NM_000377.3(WAS):c.104T>C (p.Leu35Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Unidad de Medicina Traslacional, Hospital de Ninos Ricardo Gutierrez RCV003219202 SCV003914717 likely pathogenic Wiskott-Aldrich syndrome 2021-04-14 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 35 of the WAS protein (p.Leu35Pro) resulting in a non-conservative aminoacid change predicted to be deleterious by multiple lines of computational evidence. This variant affects WH1/EVH1 domain, where most of the mutations are found in patients with Wiskott-Aldrich syndrome. The majority of mutations that impact WAS gene expression are missense mutations located within the four first exons (PMID: 15284122, PMID: 23527602). This variant is not present in population databases (gnomAD) and has not been reported in the literature in WAS-related conditions; however, a variant in the same position but causing a different aminoacid change (p.Leu35His) has been reported before (PMID: 15284122) as pathogenic and shown to lead to reduced protein expression. Based on the evidence outlined above, the variant was classified as likely pathogenic (LP) according to ACMG criteria (PP3_strong, PM5_moderate, PM1_supporting, PM2_supporting)(PMID: 25741868)

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