Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000509809 | SCV000608070 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | The p.I3103M variant (also known as c.9309A>G), located in coding exon 24 of the BRCA2 gene, results from an A to G substitution at nucleotide position 9309. The isoleucine at codon 3103 is replaced by methionine, an amino acid with highly similar properties. 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 this alteration remains unclear. |
| Color Diagnostics, |
RCV000509809 | SCV000689189 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-14 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 3103 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with ductal carcinoma (PMID: 21218378). 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. |
| Labcorp Genetics |
RCV001365159 | SCV001561412 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 3103 of the BRCA2 protein (p.Ile3103Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with personal and/or family history of breast or ovarian cancer (PMID: 28111427). ClinVar contains an entry for this variant (Variation ID: 52811). 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. |
| Breast Cancer Information Core |
RCV000114088 | SCV000147608 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2001-10-29 | no assertion criteria provided | clinical testing |