Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV004566941 | SCV005058346 | uncertain significance | Familial cancer of breast | 2024-03-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005089532 | SCV005797180 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 3018 of the BRCA2 protein (p.Ser3018Asn). 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: 91742). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Sharing Clinical Reports Project |
RCV000077650 | SCV000109453 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-03-20 | no assertion criteria provided | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000502592 | SCV000592251 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA2 p.Ser3018Asn variant was not identified in the literature nor was it identified in the Exome Variant Server, HGMD, UMD, COSMIC, LOVD or BIC databases. The p.Ser3018 residue is not highly conserved in mammals and computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. This variant occurs outside of the splicing consensus sequence and computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts no change in the splice site prediction score. In summary, based on the above information, the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown significance. |