ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1816C>T (p.Pro606Ser) (rs765924757)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000585914 SCV000694564 uncertain significance not provided 2017-01-02 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1816C>T (p.Pro606Ser) variant involves the alteration of a non-conserved nucleotide and is predicted to be damaging by 3/5 in silico tools. This variant is absent in 117916 control chromosomes from ExAC. This variant was found in one HBOC patient in literature without strong evidence for pathogenicity and they authors also classify it as a UV (unclassified variant). One internal sample carrying this variant also carries another possibly pathogenic variant BRCA1 c.2068_2082del15. Taken together, this variant is classified as Variant of Uncertain Significance
Invitae RCV000814790 SCV000955216 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 606 of the BRCA2 protein (p.Pro606Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and/or ovarian cancer in the literature and in Leiden Open-source Variation Database (PMID: 18060494, 21520333). This variant is also known as 2044C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 495434). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

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