ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9857T>A (p.Ile3286Asn)

dbSNP: rs398122624
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 RCV000164700 SCV000215368 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-15 criteria provided, single submitter clinical testing The p.I3286N variant (also known as c.9857T>A), located in coding exon 26 of the BRCA2 gene, results from a T to A substitution at nucleotide position 9857. The isoleucine at codon 3286 is replaced by asparagine, an amino acid with dissimilar properties. This alteration has been detected in 1/2575 unselected patients with breast cancer and 0/2809 healthy control individuals from a Malaysian cohort (Wen WX et al. J Med Genet, 2018 02;55:97-103). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000215513 SCV000279861 uncertain significance not provided 2024-04-25 criteria provided, single submitter clinical testing Published functional studies demonstrate lack of sensitivity to PARP inhibitors (PMID: 32444794); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as 10085T>A; This variant is associated with the following publications: (PMID: 28993434, 33471991, 31853058, 32444794, 29884841, 32377563)
Labcorp Genetics (formerly Invitae), Labcorp RCV000537252 SCV000635763 likely benign Hereditary breast ovarian cancer syndrome 2024-12-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV003460730 SCV004216127 uncertain significance Familial cancer of breast 2023-05-19 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000077053 SCV004837733 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with asparagine at codon 3286 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). A functional study has shown that this variant does not impact sensitivity to PARP inhibitors (PMID: 32444794). This variant has been reported in at least two individuals affected with breast cancer (PMID: 28993434, 33471991; Leiden Open Variation Database DB-ID BRCA2_008801). This variant has not been identified 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) RCV000077053 SCV000108850 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2011-10-28 no assertion criteria provided clinical testing

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.