Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566118 | SCV000668862 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing | The p.N986I variant (also known as c.2957A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 2957. The asparagine at codon 986 is replaced by isoleucine, an amino acid with dissimilar properties. 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. |
| Prevention |
RCV000679164 | SCV000805679 | uncertain significance | not provided | 2017-01-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000703734 | SCV000832648 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-04-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 126000). 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. 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. This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 10923033). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 986 of the BRCA2 protein (p.Asn986Ile). This variant is not present in population databases (gnomAD no frequency). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679164 | SCV002046683 | uncertain significance | not provided | 2024-02-16 | criteria provided, single submitter | clinical testing | The BRCA2 c.2957A>T (p.Asn986Ile) variant has been reported in the published literature in an individual with breast cancer as well as reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). This variant has also been reported to be located in region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). The frequency of this variant in the general population, 0.0000066 (1/152260 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| University of Washington Department of Laboratory Medicine, |
RCV000566118 | SCV003850269 | 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). |
| Breast Cancer Information Core |
RCV000113120 | SCV000146147 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2001-10-29 | no assertion criteria provided | clinical testing |