ClinVar Miner

Submissions for variant NM_000377.3(WAS):c.778-6G>A

dbSNP: rs1557007011
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519975 SCV000616916 pathogenic not provided 2017-08-02 criteria provided, single submitter clinical testing The c.778-6 G>A variant has been reported previously in association with X-linked thrombocytopenia (Albert et al., 2010; Pala et al., 2015). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.778-6 G>A creates a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. However, the variant has been observed to segregate with disease in multiple members of a large family tested at GeneDx. In summary we consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001387957 SCV001588733 pathogenic X-linked severe congenital neutropenia; Thrombocytopenia 1; Wiskott-Aldrich syndrome 2020-06-10 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the WAS gene. It does not directly change the encoded amino acid sequence of the WAS protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Wiskott-Aldrich syndrome (PMID: 20173115, 26368308, Invitae, external communication). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449116). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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