ClinVar Miner

Submissions for variant NM_000215.3(JAK3):c.1767C>T (p.Gly589=) (rs193922362)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256129 SCV000321793 pathogenic not provided 2016-08-23 criteria provided, single submitter clinical testing The c.1767 C>T variant has been published previously in association with SCID (Candotti et al., 1997; Cattaneo et al., 2013). The 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. While this variant leads to a synonymous amino acid change, several in-silico splice prediction models predict that c.1767 C>T creates a cryptic donor site which may supplant the natural donor site of intron 13 and lead to abnormal gene splicing. Additionally, functional studies have shown that the variant causes the loss of 21 nucleotides upstream of the natural splice donor site, leading to impaired function of the JAK3 protein (Candotti et al., 1997). Therefore, we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000030088 SCV000052743 likely pathogenic Severe combined immunodeficiency disease 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.

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