ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2836G>C (p.Asp946His) (rs80358534)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222307 SCV000275581 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing
Color RCV000222307 SCV000683505 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586610 SCV000694636 uncertain significance not provided 2016-10-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2836G>C (p.Asp946His) variant involves the alteration of a non-conserved nucleotide. This variant is not located in any known domain (InterPro). 4/5 in silico tools predict a damaging outcome for this variant. This variant was found in 1/120672 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported in two individuals by two clinical labs without strong evidence for pathogenicity. Multiple clinical diagnostic laboratories have classified this variant as uncertain significance. Because of the absence of sufficient clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000637635 SCV000759102 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 946 of the BRCA2 protein (p.Asp946His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs80358534, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 125996). 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: "Deleterious"; PolyPhen-2: "Probably 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.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113100 SCV000146125 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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