ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6559C>T (p.Pro2187Ser) (rs868216475)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000773213 SCV000906805 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000213792 SCV000279586 uncertain significance not provided 2015-11-10 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6559C>T at the cDNA level, p.Pro2187Ser (P2187S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). Using alternate nomenclature, this variant would be defined as BRCA2 6787C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Pro2187Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Pro2187Ser occurs at a position that is not conserved and is not located in a known functional domain (Borg 2010). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Pro2187Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000822558 SCV000963367 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-18 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2187 of the BRCA2 protein (p.Pro2187Ser). The proline residue is moderately 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 not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 234614). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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