ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7525A>G (p.Ser2509Gly)

dbSNP: rs1555286268
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001060288 SCV001224965 uncertain significance Hereditary breast ovarian cancer syndrome 2019-04-24 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with glycine at codon 2509 of the BRCA2 protein (p.Ser2509Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine.
Ambry Genetics RCV002393293 SCV002675121 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-16 criteria provided, single submitter clinical testing The p.S2509G variant (also known as c.7525A>G), located in coding exon 14 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7525. The serine at codon 2509 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.S2509G remains unclear.
GeneDx RCV003227906 SCV003924569 uncertain significance not provided 2022-11-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 7753A>G; This variant is associated with the following publications: (PMID: 31911673, 12228710)

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.