ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1564G>C (p.Gly522Arg) (rs80358442)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165147 SCV000215858 likely benign Hereditary cancer-predisposing syndrome 2017-11-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034431 SCV000043198 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000031327 SCV000145889 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000165147 SCV000902872 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-24 criteria provided, single submitter clinical testing
Counsyl RCV000031327 SCV000785157 uncertain significance Breast-ovarian cancer, familial 2 2017-05-16 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000200975 SCV000591753 uncertain significance not specified 2013-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000200975 SCV000210273 likely benign not specified 2017-12-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000034431 SCV000694545 uncertain significance not provided 2016-03-31 criteria provided, single submitter clinical testing Variant summary: This c.1564G>C variant affects a not conserved nucleotide, resulting in amino acid change from Gly to Arg. 3/5 in-silico tools predict this variant to be benign. This variant was found in 2/121584 control chromosomes including the large and broad populations of ExAC at a frequency of 0.0000164, which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503) in this gene. This variant has been reported in one HBOC family in literature without a strong evidence for causality. It has also been reported in multiple individuals undergoing BRCA1/2 testing by clinical labs and databases. The variant has been reported to co-occur with BRCA1 truncating variants p.Gln1420X (via UMD) and p.Trp1712X (via BIC), suggesting the variant to be benign. Two out of four labs have also classified this variant as likely benign (the rest two classify it as uncertain significance). Taken together, this variant has currently been classified as VUS Possibly Benign.
Invitae RCV000043829 SCV000071842 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 522 of the BRCA2 protein (p.Gly522Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs80358442, ExAC 0.009%). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 22476429, 24916970). ClinVar contains an entry for this variant (Variation ID: 37746). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV000043829 SCV000838761 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031327 SCV000053932 uncertain significance Breast-ovarian cancer, familial 2 2010-10-01 no assertion criteria provided clinical testing

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