ClinVar Miner

Submissions for variant NM_006949.4(STXBP2):c.914A>G (p.Glu305Gly)

gnomAD frequency: 0.00015  dbSNP: rs370890802
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000281145 SCV000415681 uncertain significance Familial hemophagocytic lymphohistiocytosis 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000927651 SCV001073239 likely benign Familial hemophagocytic lymphohistiocytosis 5 2024-01-28 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821004 SCV002065234 uncertain significance not specified 2021-11-10 criteria provided, single submitter clinical testing DNA sequence analysis of the STXBP2 gene demonstrated a sequence change, c.914A>G, in exon 11 that results in an amino acid change, p.Glu305Gly. This sequence change has been described in the gnomAD database with a frequency of 0.55% in the Ashkenazi Jewish subpopulation (dbSNP rs370890802). The p.Glu305Gly change affects a moderately conserved amino acid residue located in a domain of the STXBP2 protein that is known to be functional. The p.Glu305Gly substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with STXBP2-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Glu305Gly change remains unknown at this time.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001821004 SCV004021064 uncertain significance not specified 2023-06-28 criteria provided, single submitter clinical testing Variant summary: STXBP2 c.914A>G (p.Glu305Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 250586 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in STXBP2 causing Familial Hemophagocytic Lymphohistiocytosis (0.00028 vs 0.0022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.914A>G in individuals affected with Familial Hemophagocytic Lymphohistiocytosis and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance and one as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences RCV003922410 SCV004750362 likely benign STXBP2-related disorder 2023-05-24 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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