ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4915G>A (p.Val1639Ile) (rs80358716)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083151 SCV000072532 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129029 SCV000172937 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240704 SCV000265941 uncertain significance Breast neoplasm 2015-11-01 criteria provided, single submitter research
Counsyl RCV000031513 SCV000488073 uncertain significance Breast-ovarian cancer, familial 2 2015-12-30 criteria provided, single submitter clinical testing
GeneDx RCV000587911 SCV000512365 likely benign not provided 2020-01-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22811390, 10923033, 24916970, 22476429, 27257965, 24817641, 30287823, 30702160, 31131967, 30410429, 31825140)
Color Health, Inc RCV000129029 SCV000537492 likely benign Hereditary cancer-predisposing syndrome 2015-07-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587911 SCV000694811 likely benign not provided 2017-02-15 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4915G>A (p.Val1639Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was observed in the large and broad control population from ExAC with an allele frequency of 1/119,420 control chromosomes which does not exceed the predicted maximum expected allele frequency for a pathogenic BRCA2 variant of 1/1,333. The variant of interest has been reported in affected individuals via publications, although with limited information (ie lack of co-occurrence and co-segregation data). However, a reputable database cites the variant to co-occur with potentially pathogenic BRCA1 variants, c.2457delC (p.Asp821fsX25 pathogenic in GE) and exon13ins6kb, along with an internal LCA sample reporting the variant to co-occur with another pathogenic BRCA2 variant, c.5073dupA (p.Trp1692fsX3 pathogenic in GE). In addition, multiple reputable clinical laboratories cite the variant with a classification of "benign." Considering all available information, the variant of interest is classified as Likely Benign.
Research and Development, ARUP Laboratories RCV001642351 SCV001854817 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031513 SCV000054118 benign Breast-ovarian cancer, familial 2 2009-11-11 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031513 SCV000146505 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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