ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8153T>C (p.Ile2718Thr)

gnomAD frequency: 0.00001  dbSNP: rs80359060
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000045432 SCV000073445 likely benign Hereditary breast ovarian cancer syndrome 2025-01-17 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000583191 SCV000689100 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-18 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 2718 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 14 individuals affected with breast cancer, however, it is described as a polymorphism and the status of covariants was not provided (PMID: 20859677, 23096355). This variant has been identified in 2/251248 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl RCV000031722 SCV000786481 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2018-05-08 criteria provided, single submitter clinical testing
Mendelics RCV000031722 SCV001139207 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000583191 SCV001189752 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-30 criteria provided, single submitter clinical testing The p.I2718T variant (also known as c.8153T>C), located in coding exon 17 of the BRCA2 gene, results from a T to C substitution at nucleotide position 8153. The isoleucine at codon 2718 is replaced by threonine, an amino acid with similar properties. This alteration has been identified in multiple individuals diagnosed with breast cancer (Lara K et al. Biol. Res. 2012;45:117-30; Alvarez C et al. Oncotarget, 2017 Sep;8:74233-74243). Of note, this alteration is also known as 8381T>C in published literature. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV002305440 SCV002599649 uncertain significance not provided 2022-11-01 criteria provided, single submitter clinical testing Observed in individuals with breast cancer (Gonzalez-Hormazabal et al., 2011; Lara K et al., 2012; Alvarez et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 8381T>C; This variant is associated with the following publications: (PMID: 29088781, 19043619, 23096355, 20859677, 12228710, 32377563, 29884841)
All of Us Research Program, National Institutes of Health RCV004803076 SCV005425788 uncertain significance BRCA2-related cancer predisposition 2024-03-24 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 2718 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 14 individuals affected with breast cancer, however, it is described as a polymorphism and the status of covariants was not provided (PMID: 20859677, 23096355). This variant has been identified in 2/251248 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031722 SCV000054329 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2010-05-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031722 SCV000147283 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2003-12-23 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000031722 SCV004243804 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2020-03-02 no assertion criteria provided clinical testing

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