ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7630G>A (p.Gly2544Ser) (rs587781485)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129445 SCV000184215 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000161933 SCV000211918 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2544 of the BRCA2 protein (p.Gly2544Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 141088). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Counsyl RCV000662876 SCV000785774 uncertain significance Breast-ovarian cancer, familial 2 2017-11-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656622 SCV000858442 uncertain significance not provided 2017-12-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000656622 SCV000883515 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781086 SCV000918898 uncertain significance not specified 2017-11-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7630G>A (p.Gly2544Ser) variant involves the alteration of a conserved nucleotide and is predicted to be damaging by 5/5 in silico tools. This variant is absent in 245794 control chromosomes (gnomAD). It has been reported to co-occur with another pathogenic variant in BRCA1 gene in a clinical sample in literature (Schenk_2017) and one internal sample undergoing for BRCA1/2 testing. Whether these samples are independent cannot be validated at this time. Multiple clinical diagnostic laboratories have classified this variant as uncertain significance. Two other missense variants in this codon (G2544D and G2544R) have been classified as uncertain significance by clinical laboratories. Taken together, this variant is classified as Variant of Uncertain Significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656622 SCV000778713 uncertain significance not provided 2017-12-07 no assertion criteria provided clinical testing

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