ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5191C>A (p.His1731Asn)

gnomAD frequency: 0.00001  dbSNP: rs80358745
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000167854 SCV000072613 likely benign Hereditary breast ovarian cancer syndrome 2024-12-18 criteria provided, single submitter clinical testing
GeneDx RCV000586989 SCV000210346 likely benign not provided 2019-03-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20406939)
Ambry Genetics RCV000222021 SCV000272933 likely benign Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Counsyl RCV000077348 SCV000784948 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2017-02-16 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000222021 SCV000910981 likely benign Hereditary cancer-predisposing syndrome 2017-07-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586989 SCV002046249 uncertain significance not provided 2024-02-12 criteria provided, single submitter clinical testing The BRCA2 c.5191C>A (p.His1731Asn) variant has been reported in the published literature in individuals affected with ovarian cancer (PMID: 20406939 (2010)). In a large breast cancer association study, the variant was reported in individuals with breast cancer as well as in a reportedly healthy individual (PMID: 33471991 (2021), https://databases.lovd.nl/shared/variants/BRCA2), and described to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). The frequency of this variant in the general population, 0.000045 (5/111278 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
University of Washington Department of Laboratory Medicine, University of Washington RCV000222021 SCV003847064 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003492354 SCV004240321 uncertain significance Breast and/or ovarian cancer 2023-05-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000077348 SCV004845780 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2023-12-13 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077348 SCV000109145 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2012-06-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077348 SCV000146560 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2007-01-18 no assertion criteria provided clinical testing

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