ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9917C>T (p.Thr3306Ile) (rs80359250)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045913 SCV000073926 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-07-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 3306 of the BRCA2 protein (p.Thr3306Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, this variant occurs with a pathogenic variant in BRCA2 in this individual. While it is unknown if these variants are on the same or opposite chromosomes, this observation suggests that the c.9917C>T variant is not a primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 52915). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000112822 SCV000145729 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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