Submissions for variant NM_000377.3(WAS):c.121C>T (p.Arg41Ter)

dbSNP: rs11545907

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001216267	SCV001388055	pathogenic	X-linked severe congenital neutropenia; Thrombocytopenia 1; Wiskott-Aldrich syndrome	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg41*) in the WAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WAS are known to be pathogenic (PMID: 15284122). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 945596). This variant is also known as 155C>T. This premature translational stop signal has been observed in individual(s) with Wiskott-Aldrich syndrome (PMID: 8528198, 15497008, 21185603, 25862925, 27566838).
PreventionGenetics, part of Exact Sciences	RCV003908449	SCV004727282	pathogenic	WAS-related disorder	2024-01-29	no assertion criteria provided	clinical testing	The WAS c.121C>T variant is predicted to result in premature protein termination (p.Arg41*). This variant has been reported to be causative for Wiskott-Aldrich syndrome (Kolluri et al. 1995. PubMed ID: 8528198; Gulácsy et al. 2010. PubMed ID: 21185603; Vignesh et al. 2016. PubMed ID: 27566838). This variant has also been reported in individuals with suspected primary immunodeficiency (Platt et al. 2020. PubMed ID: 32888943. Table E2). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in WAS are expected to be pathogenic. This variant is interpreted as pathogenic.