Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567399 | SCV000668688 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-01 | criteria provided, single submitter | clinical testing | The p.S2554G variant (also known as c.7660A>G), located in coding exon 15 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7660. The serine at codon 2554 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV000798016 | SCV000937608 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 2554 of the BRCA2 protein (p.Ser2554Gly). 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. ClinVar contains an entry for this variant (Variation ID: 252847). 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. |
| Gene |
RCV003320622 | SCV004025314 | uncertain significance | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 7888A>G; This variant is associated with the following publications: (PMID: 31131967, 12228710) |
| All of Us Research Program, |
RCV000238966 | SCV004844451 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-12-18 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with glycine at codon 2554 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0246 and 0.901, respectively (PMID: 31131967). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800363 | SCV005423494 | uncertain significance | not specified | 2024-10-03 | criteria provided, single submitter | clinical testing | |
| Sharing Clinical Reports Project |
RCV000238966 | SCV000297450 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2011-05-02 | no assertion criteria provided | clinical testing |