Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000554176 | SCV000635542 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-08-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with threonine at codon 2295 of the BRCA2 protein (p.Arg2295Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a healthy individual with a family history of breast cancer (PMID: 22366370). ClinVar contains an entry for this variant (Variation ID: 462419). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. 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. |
Color Diagnostics, |
RCV000777234 | SCV000912925 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-06 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with threonine at codon 2295 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with a personal or family history of breast and/or ovarian cancer (PMID: 22366370). 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. |
Ambry Genetics | RCV000777234 | SCV002662921 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-18 | criteria provided, single submitter | clinical testing | The p.R2295T variant (also known as c.6884G>C), located in coding exon 11 of the BRCA2 gene, results from a G to C substitution at nucleotide position 6884. The arginine at codon 2295 is replaced by threonine, an amino acid with similar properties. This alteration was identified in an individual with a family history of breast cancer (Levanat S et al. Gene, 2012 May;498:169-76). This amino acid position is 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. |
MGZ Medical Genetics Center | RCV003607300 | SCV004543913 | likely benign | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP |
All of Us Research Program, |
RCV003999066 | SCV004844326 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-08-28 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with threonine at codon 2295 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with a personal or family history of breast and/or ovarian cancer (PMID: 22366370). 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. |