ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3824T>C (p.Ile1275Thr) (rs80358625)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044272 SCV000072285 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1275 of the BRCA2 protein (p.Ile1275Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs80358625, ExAC <0.01%). This variant has been reported in an individual with a personal or family history of breast cancer (PMID: 25896959). This variant has also been observed in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, in that individual, a pathogenic allele was also identified in the BRCA1 gene, which suggests that this c.3824T>C variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 51531). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The threonine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV000132466 SCV000187560 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Counsyl RCV000083101 SCV000786462 uncertain significance Breast-ovarian cancer, familial 2 2018-05-07 criteria provided, single submitter clinical testing
Color RCV000132466 SCV000903954 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985512 SCV001133772 uncertain significance not provided 2018-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001112374 SCV001270028 uncertain significance Fanconi anemia, complementation group D1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000083101 SCV001270029 uncertain significance Breast-ovarian cancer, familial 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharing Clinical Reports Project (SCRP) RCV000083101 SCV000115175 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083101 SCV000146303 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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