ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5191C>A (p.His1731Asn) (rs80358745)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222021 SCV000272933 likely benign Hereditary cancer-predisposing syndrome 2015-11-18 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077348 SCV000146560 uncertain significance Breast-ovarian cancer, familial 2 2007-01-18 no assertion criteria provided clinical testing
Color RCV000222021 SCV000910981 likely benign Hereditary cancer-predisposing syndrome 2017-07-26 criteria provided, single submitter clinical testing
Counsyl RCV000077348 SCV000784948 uncertain significance Breast-ovarian cancer, familial 2 2017-02-16 criteria provided, single submitter clinical testing
GeneDx RCV000044600 SCV000210346 likely benign not specified 2018-02-14 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 RCV000167854 SCV000494414 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-02-29 criteria provided, single submitter clinical testing Variant summary: This c.5191C>A variant affects a non-conserved nucleotide, resulting in amino acid change from His to Asn. 4/4 in-silico tools used predict this variant to be benign. This variant was found in 1/119192 control chromosomes at a frequency of 0.0000084, which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503). This variant has been reported in one ovarian cancer patient without strong evidence of pathogenicity. Multiple clinical labs and a reputable database have classified this variant as having uncertain significance. Because of the limited clinical information and the lack of functional studies, the variant has currently been classified as a variant of uncertain significance (VUS) until additional information becomes available.
Integrated Genetics/Laboratory Corporation of America RCV000586989 SCV000694839 uncertain significance not provided 2016-02-29 criteria provided, single submitter clinical testing Variant summary: This c.5191C>A variant affects a non-conserved nucleotide, resulting in amino acid change from His to Asn. 4/4 in-silico tools used predict this variant to be benign. This variant was found in 1/119192 control chromosomes at a frequency of 0.0000084, which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503). This variant has been reported in one ovarian cancer patient without strong evidence of pathogenicity. Multiple clinical labs and a reputable database have classified this variant as having uncertain significance. Because of the limited clinical information and the lack of functional studies, the variant has currently been classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000167854 SCV000072613 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change replaces histidine with asparagine at codon 1731 of the BRCA2 protein (p.His1731Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is present in population databases (rs80358745, ExAC 0.002%). This variant has been reported in an individual affected with ovarian cancer (PMID: 20406939). ClinVar contains an entry for this variant (Variation ID: 51811). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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) RCV000077348 SCV000109145 likely benign Breast-ovarian cancer, familial 2 2012-06-06 no assertion criteria provided clinical testing

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