ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8386C>T (p.Pro2796Ser) (rs146120136)

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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 RCV000130261 SCV000185105 likely benign Hereditary cancer-predisposing syndrome 2018-02-06 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)
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735611 SCV000901123 uncertain significance Breast and/or ovarian cancer 2017-06-09 criteria provided, single submitter clinical testing
Color RCV000130261 SCV000903472 benign Hereditary cancer-predisposing syndrome 2016-04-26 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735611 SCV000863749 uncertain significance Breast and/or ovarian cancer no assertion criteria provided clinical testing
GeneDx RCV000435429 SCV000516170 likely benign not specified 2017-10-25 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 RCV000586491 SCV000695148 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing Variant summary: The c.8386C>T (p.Pro2796Ser) in BRCA2 gene is a missense variant involves a non-conserved nucleotide and 3/5 in silico tools predict benign outcome. The variant is located within the close proximity to the second OB fold (OB2) of the 800-amino acid C-terminal ssDNA binding domain (DBD) of BRCA2, however no functional studies confirming an effect of this change on the protein function were published at the time of evaluation. The variant was proven to not affect splicing. The variant is present at a low frequencies in the control population datasets of ExAC and gnomAD (1.647e-05; 2/121408 and 4/246222 chrs tested, respectively). These frequencies do not exceed the maximal expected allele frequency for a disease causing allele in BRCA2 gene (0.000175). The variant has been reported in several affected individuals via published reports without strong evidence for causality. Lastly, several reputable databases/clinical laboratories have classified the variant as VUS/Likely Benign. Taken together, the variant was classified as VUS, until new information becomes available.
Invitae RCV000226735 SCV000283341 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-08-29 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2796 of the BRCA2 protein (p.Pro2796Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs146120136, ExAC 0.003%). This variant has been observed in individuals affected with breast cancer (PMID: 24094589, 25428789). This variant is also known as c.8614C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 91511). 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 serine 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000435429 SCV000600801 uncertain significance not specified 2017-02-06 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077028 SCV000108825 likely benign Breast-ovarian cancer, familial 2 2011-04-19 no assertion criteria provided clinical testing

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