ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5278T>G (p.Ser1760Ala) (rs28897735)

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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 RCV000131676 SCV000186712 likely benign Hereditary cancer-predisposing syndrome 2017-10-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Does not segregate with disease in family study (genes with incomplete penetrance)
Color RCV000131676 SCV000911758 likely benign Hereditary cancer-predisposing syndrome 2017-08-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000440605 SCV000591957 uncertain significance not specified 2013-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000440605 SCV000516136 likely benign not specified 2017-12-22 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 RCV000440605 SCV000916887 uncertain significance not specified 2017-11-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5278T>G (p.Ser1760Ala) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict benign outcome for this variant. This variant was found in 8/245672 control chromosomes (including gnomAD) at a frequency of 0.0000326, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multifactorial likelihood and genetic analysis for this variant by three studies shows that it has low odds in favor of causality, thus leading to the classification of likely benign by two studies (Vallee_2012, Lindor_2012). Multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign(2) as well as uncertain significance(3). Taken together, this variant is classified as VUS-possibly benign.
Invitae RCV000476848 SCV000549865 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 1760 of the BRCA2 protein (p.Ser1760Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is present in population databases (rs28897735, ExAC 0.009%). 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: 91410). Based on a multifactorial likelihood algorithm using genetic, in silico, and statistical data, this variant has been determined to have a low probability of being pathogenic (PMID: 21990134). 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.
Sharing Clinical Reports Project (SCRP) RCV000076927 SCV000108724 uncertain significance Breast-ovarian cancer, familial 2 2011-04-25 no assertion criteria provided clinical testing

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