Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215878 | SCV000278256 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-09-10 | criteria provided, single submitter | clinical testing | The p.S2071I variant (also known as c.6212G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 6212. The serine at codon 2071 is replaced by isoleucine, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs80358861. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.S2071I remains unclear. |
| Labcorp Genetics |
RCV001373292 | SCV001570000 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2071 of the BRCA2 protein (p.Ser2071Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 52034). 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000215878 | SCV003852322 | 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 |
RCV000113548 | SCV000146793 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 1997-11-13 | no assertion criteria provided | clinical testing |