ClinVar Miner

Submissions for variant NM_000377.2(WAS):c.273+10_273+11dup (rs58371799)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238722 SCV000296909 benign not specified 2015-10-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV000633310 SCV000754527 benign Severe congenital neutropenia X-linked; Thrombocytopenia, X-linked; Wiskott-Aldrich syndrome 2017-12-18 criteria provided, single submitter clinical testing
PreventionGenetics RCV000238722 SCV000303901 likely benign not specified criteria provided, single submitter clinical testing

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