ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9812T>C (p.Leu3271Ser) (rs397507436)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130205 SCV000185043 uncertain significance Hereditary cancer-predisposing syndrome 2014-03-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000759695 SCV000293921 uncertain significance not provided 2016-02-05 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9812T>C at the cDNA level, p.Leu3271Ser (L3271S) at the protein level, and results in the change of a Leucine to a Serine (TTG>TCG). Using alternate nomenclature, this variant would be defined as BRCA2 10040T>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Leu3271Ser 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 Leucine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Leu3271Ser occurs at a position where amino acids with properties similar to Leucine are tolerated across species and is located within the Cyclin A binding domain (Esashi 2005). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Leu3271Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000457079 SCV000549704 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-25 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 3271 of the BRCA2 protein (p.Leu3271Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine 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: 38264). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759695 SCV000889192 uncertain significance not provided 2018-05-25 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031847 SCV000054455 uncertain significance Breast-ovarian cancer, familial 2 2012-10-16 no assertion criteria provided clinical testing

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