Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220788 | SCV000275698 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-08 | criteria provided, single submitter | clinical testing | The p.S1907T variant (also known as c.5719T>A or 5947T>A), located in coding exon 10 of the BRCA2 gene, results from a T to A substitution at nucleotide position 5719. The serine at codon 1907 is replaced by threonine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage of 6,503 at this position. 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.S1907T remains unclear. |
| University of Washington Department of Laboratory Medicine, |
RCV000220788 | SCV003849046 | 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). |
| Labcorp Genetics |
RCV003644942 | SCV004459429 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-20 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 231754). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1907 of the BRCA2 protein (p.Ser1907Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. |