ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9253A>C (p.Thr3085Pro) (rs397507423)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000439515 SCV000602829 likely benign not specified 2016-11-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509957 SCV000608022 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000509957 SCV000908252 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000439515 SCV000592266 likely benign not specified 2013-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000439515 SCV000523999 likely benign not specified 2017-07-03 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 RCV000587457 SCV000695223 likely benign not provided 2016-06-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9253A>C (p.Thr3085Pro) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome. This variant was found in 1/119814 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been found to co-occur in cis with a pathogenic mutation BRCA2 c.9235delG (p.Val3079PhefsX4) in an LCA sample, suggesting the benign role of the variant. One clinical diagnostic laboratories/reputable databases classified this variant as a VUS. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000557691 SCV000635726 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with proline at codon 3085 of the BRCA2 protein (p.Thr3085Pro). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and proline. This variant is present in population databases (rs397507423, ExAC 0.009%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 38224). 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 proline 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.
Sharing Clinical Reports Project (SCRP) RCV000031807 SCV000054415 uncertain significance Breast-ovarian cancer, familial 2 2009-01-08 no assertion criteria provided clinical testing

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