Submissions for variant NM_002351.5(SH2D1A):c.102C>A (p.Ser34Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003041478	SCV003445841	uncertain significance	X-linked lymphoproliferative disease due to SH2D1A deficiency	2022-02-19	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ser34 amino acid residue in SH2D1A. Other variant(s) that disrupt this residue have been observed in individuals with SH2D1A-related conditions (PMID: 12356686, 15632210), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with X-linked lymphoproliferative disease (PMID: 15632210). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 34 of the SH2D1A protein (p.Ser34Arg).
GeneDx	RCV003236948	SCV003935855	likely pathogenic	not provided	2023-06-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20660790, 15632210)