ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3071T>C (p.Ile1024Thr) (rs764921920)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564299 SCV000661343 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000564299 SCV000683525 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing
Counsyl RCV000662817 SCV000785658 uncertain significance Breast-ovarian cancer, familial 2 2017-10-19 criteria provided, single submitter clinical testing
GeneDx RCV000587236 SCV000566331 uncertain significance not provided 2018-06-11 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3071T>C at the cDNA level, p.Ile1024Thr (I1024T) at the protein level, and results in the change of an Isoleucine to a Threonine (ATT>ACT). Using alternate nomenclature, this variant would be defined as BRCA2 3299T>C. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Ile1024Thr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the BRC1 domain and the RAD51 binding domain (Cole 2011, Roy 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA2 Ile1024Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000587236 SCV000694662 uncertain significance not provided 2016-03-08 criteria provided, single submitter clinical testing Variant summary: c.3071T>C affects a conserved nucleotide, resulting in amino acid change from Ile to Thr. 3/4 in-silico tools predict this variant to be damaging (SNPs&GO not captured due to low reliability index). This variant was not found in 120292 control chromosomes. The variant of interest has not been reported in affected individuals via publications and/or reputable databases; nor evaluated for functional impact by in vivo/vitro studies. One clinical lab classified this variant as VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000167880 SCV000218526 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1024 of the BRCA2 protein (p.Ile1024Thr). The Ile1024 residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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. ClinVar contains an entry for this variant (Variation ID: 188062). 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"; MutationTaster: "polymorphism"; Align-GVGD: "C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.