ClinVar Miner

Submissions for variant NM_002351.4(SH2D1A):c.163C>T (p.Arg55Ter) (rs111033623)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV001270156 SCV000697917 pathogenic X-Linked Lymphoproliferative Syndrome 2017-05-19 criteria provided, single submitter clinical testing Variant summary: The SH2D1A c.163C>T (p.Arg55X) variant results in a premature termination codon, predicted to cause a truncated or absent SH2D1A protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Functional studies showed no signaling lymphocyte activation moleculeassociated protein (SAP) expression in NK cells and no (or limited) expression in T cells in XLP patients. One truncation downstream of this position has been classified as pathogenic by our laboratory (e.g. c.191G>A, p.Trp64X). One in silico tool predicts a damaging outcome for this variant. The variant of interest was absent in a large, broad control population, ExAC in 0/87863 control chromosomes. This variant was found in multiple patients with XLP (Marsh_SH2S1A_BioBlood&MarrowTranspl_2014, Chen_ItJouPed_2016, Palendira_JEM_2012). Multiple clinical diagnostic laboratories/reputable databases (including OMIM) classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000011645 SCV000766629 pathogenic Lymphoproliferative syndrome 1, X-linked 2019-09-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg55*) in the SH2D1A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals and families affected with X-linked lymphoproliferative disease (PMID: 11520777, 19621458, 9771704). It has also been reporeted in individuls affected with Burkitt s lymphoma and haemophagocytic lymphohistiocytosis (PMID: 24923536, 27209435). This variant is also known as C462T in the literature. ClinVar contains an entry for this variant (Variation ID: 10898). Loss-of-function variants in SH2D1A are known to be pathogenic (PMID: 9771704, 11049992, 15711562). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091713 SCV001247906 pathogenic not provided 2019-11-01 criteria provided, single submitter clinical testing
OMIM RCV000011645 SCV000031877 pathogenic Lymphoproliferative syndrome 1, X-linked 2000-03-05 no assertion criteria provided literature only

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