ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4534C>T (p.Arg1512Cys) (rs80358684)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044428 SCV000072441 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-10-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1512 of the BRCA2 protein (p.Arg1512Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs80358684, ExAC 0.002%). This variant has been observed in individuals affected with breast cancer, malignant melanoma, and stomach cancer (PMID: 30287823, 30286154, 26689913). ClinVar contains an entry for this variant (Variation ID: 51660). 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 cysteine 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.
Ambry Genetics RCV000130950 SCV000185864 likely benign Hereditary cancer-predisposing syndrome 2019-07-17 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
Counsyl RCV000113312 SCV000785700 uncertain significance Breast-ovarian cancer, familial 2 2017-11-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755874 SCV000883512 uncertain significance not provided 2017-11-08 criteria provided, single submitter clinical testing
Color RCV000130950 SCV000903514 likely benign Hereditary cancer-predisposing syndrome 2017-03-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113312 SCV001271520 uncertain significance Breast-ovarian cancer, familial 2 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001113729 SCV001271521 uncertain significance Fanconi anemia, complementation group D1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113312 SCV000146438 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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