ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3262C>T (p.Pro1088Ser) (rs80358572)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129258 SCV000184018 likely benign Hereditary cancer-predisposing syndrome 2017-09-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031410 SCV000146198 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129258 SCV000902754 benign Hereditary cancer-predisposing syndrome 2016-06-22 criteria provided, single submitter clinical testing
Counsyl RCV000031410 SCV000488689 uncertain significance Breast-ovarian cancer, familial 2 2016-05-26 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031410 SCV000744436 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000044159 SCV000210587 likely benign not specified 2017-07-21 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000031410 SCV000743282 likely benign Breast-ovarian cancer, familial 2 2015-06-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000585942 SCV000694684 likely benign not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3262C>T (p.Pro1088Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant does not fall within a known functional domain and 3/5 in silico tools predict a benign outcome. This variant was found in the large control population database ExAC at a frequency of 0.0000085 (1/118202 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant of interest was reported to occur somatically in non-MSI positive samples from patients with esophageal adenocarcinoma and in the MSI instable FFPE specimen derived from a patient with hereditary endometrial carcinoma in whom a germline pathogenic variant in the MSH6 gene had been identified (patient 5, MSI unstable, MSH6 variant c.3729_3732dupATTA). The reports on germline occurrence of this variant do not provide sufficient evidence to unequivocally rule in our rule out causality. The BIC database shows the variant associated with 8 individuals, 4 of whom have multiple co-occuring pathogenic/likely pathogenic BRCA1 mutations (2 - exon13ins6kb, 1 - c.3549_3550delinsT (p.K1183fsX), and 1 - c.4357+1G>A). Multiple clinical diagnostic laboratories/reputable databases have conflicting classifications for the variant, including benign (2x), likely benign (2x), and uncertain significance (2x). Taken together, based on at-least 5 reports of the occurrence of this variant in patients with an alternative molecular basis of disease attributed to mutations in MSH6 (n=1) or BRCA1 (n=4) genes, this variant is classified as "Likely Benign" until additional functional studies demonstrating no functional impact and a larger prevalence in the control cohorts are obtained.
Invitae RCV000195328 SCV000072172 benign Hereditary breast and ovarian cancer syndrome 2017-11-07 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000585942 SCV000778661 likely benign not provided 2017-07-27 no assertion criteria provided clinical testing
PreventionGenetics RCV000585942 SCV000805688 uncertain significance not provided 2018-01-10 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031410 SCV000054015 benign Breast-ovarian cancer, familial 2 2008-10-01 no assertion criteria provided clinical testing

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