ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2489A>T (p.Asn830Ile)

dbSNP: rs786202809
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637393 SCV000758849 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 830 of the BRCA2 protein (p.Asn830Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 23633455). ClinVar contains an entry for this variant (Variation ID: 531236). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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.
GeneDx RCV001756058 SCV002007323 uncertain significance not provided 2019-06-10 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002424403 SCV002741784 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-03 criteria provided, single submitter clinical testing The p.N830I variant (also known as c.2489A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 2489. The asparagine at codon 830 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is poorly 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002424403 SCV003848361 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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