ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3310A>C (p.Thr1104Pro) (rs80358577)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163592 SCV000214154 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000083097 SCV000146212 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000163592 SCV000906661 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781094 SCV000918914 uncertain significance not specified 2018-06-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3310A>C (p.Thr1104Pro) results in a non-conservative amino acid change located in the outside of any known functional domain or repeat of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 231484 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3310A>C has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.5289delG, p.Leu1764fsX1), providing supporting evidence for a benign role. In addition, all patients with c.3310A>C, reported in BIC (x4) and UMD (x3) also carrying BRCA2 c.3503T>A (M1168K), suggesting in cis phase for these two variants. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000044176 SCV000072189 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-19 criteria provided, single submitter clinical testing This sequence change replaces threonine with proline at codon 1104 of the BRCA2 protein (p.Thr1104Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline. This variant is present in population databases (rs80358577, ExAC 0.002%). This variant has been reported in an individual with a personal or family history of breast cancer (PMID: 22977638). This variant is also known as 3538A>C in the literature. ClinVar contains an entry for this variant (Variation ID: 51448). 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: "Deleterious"; 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 RCV000758881 SCV000887787 uncertain significance not provided 2017-12-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083097 SCV000115171 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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