Submissions for variant NM_000377.3(WAS):c.273+10_273+11dup

dbSNP: rs58371799

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000238722	SCV000053271	benign	not specified	2018-09-12	criteria provided, single submitter	clinical testing	Variant summary: WAS c.273+10_273+11dupCC alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0046 in 176885 control chromosomes, predominantly at a frequency of 221 within the East Asian subpopulation in the gnomAD database, including 25 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 62508.24 fold of the estimated maximal expected allele frequency for a pathogenic variant in WAS causing Wiskott-Aldrich Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.273+10_273+11dupCC in individuals affected with Wiskott-Aldrich Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238722	SCV000296909	benign	not specified	2015-10-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000238722	SCV000303901	likely benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000633310	SCV000754527	benign	X-linked severe congenital neutropenia; Thrombocytopenia 1; Wiskott-Aldrich syndrome	2025-02-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001725936	SCV001988838	benign	not provided	2021-08-13	criteria provided, single submitter	clinical testing	In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 30738478)
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000238722	SCV001808754	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001725936	SCV001967593	likely benign	not provided		no assertion criteria provided	clinical testing