ClinVar Miner

Submissions for variant NM_006949.4(STXBP2):c.1501G>A (p.Asp501Asn)

gnomAD frequency: 0.00001  dbSNP: rs776782833
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001822455 SCV002071397 uncertain significance not specified 2021-03-24 criteria provided, single submitter clinical testing DNA sequence analysis of the STXBP2 gene demonstrated a sequence change, c.1501G>A, in exon 17 that results in an amino acid change, p.Asp501Asn. This sequence change has been described in gnomAD with a low frequency of 0.0019% (dbSNP rs776782833) in the Non-Finnish European sub-population. The p.Asp501Asn change affects a moderately conserved amino acid residue located in a domain of the STXBP2 protein that is known to be functional. The p.Asp501Asn 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 patients with STXBP2-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Asp501Asn change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869756 SCV002222727 uncertain significance Familial hemophagocytic lymphohistiocytosis 5 2022-07-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 501 of the STXBP2 protein (p.Asp501Asn). This variant is present in population databases (rs776782833, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with STXBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1337857). 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 tolerated. 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.
Ambry Genetics RCV002542652 SCV003659926 uncertain significance Inborn genetic diseases 2022-11-07 criteria provided, single submitter clinical testing The c.1501G>A (p.D501N) alteration is located in exon 17 (coding exon 17) of the STXBP2 gene. This alteration results from a G to A substitution at nucleotide position 1501, causing the aspartic acid (D) at amino acid position 501 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.