ClinVar Miner

Submissions for variant NM_000377.2(WAS):c.777+1G>A (rs1057517845)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413782 SCV000490880 pathogenic not provided 2015-05-21 criteria provided, single submitter clinical testing The c.777+1 G>A splice site variant in the WAS gene has been previously reported in association with Wiskott-Aldrich syndrome using alternative nomenclature (Schindelhauer et al.,1996). This variant destroys the canonical splice donor site in intron 8, and is expected to cause abnormal gene splicing. Alternative variants at the same splice donor site (c.777+1 G>C, c.777+5 G>C) have been reported in the Human Gene Mutation Database in association with WAS (Stenson et al., 2014). The c.777+1 G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.777+1 to be a pathogenic variant.
Invitae RCV000461952 SCV000551383 pathogenic Severe congenital neutropenia X-linked; Thrombocytopenia, X-linked; Wiskott-Aldrich syndrome 2017-03-01 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 8 of the WAS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in the literature in individuals affected with classical Wiskott-Aldrich syndrome, (PMID: 8682510). This variant is also known as 811+1G>A in the literature. An experimental study has shown that this variant disrupts RNA splicing in the lymphocytes of the patient. For these reasons, this variant has been classified as Pathogenic.

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