Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001018476 | SCV001179721 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | The p.K1025N variant (also known as c.3075G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 3075. The lysine at codon 1025 is replaced by asparagine, an amino acid with similar properties. This alteration was identified in an individual with a family history of breast and/or ovarian cancer from Slovakia (Konecny M et al. Breast Cancer Res Treat, 2011 Feb;126:119-30). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV001018476 | SCV003850363 | 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). |
All of Us Research Program, |
RCV000113131 | SCV004845102 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-10-27 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 1025 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with breast or ovarian cancer; this individual carried a second BRCA2 variant known to be pathogenic that could explain the observed phenotype (PMID: 16168118). 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. |
Breast Cancer Information Core |
RCV000113131 | SCV000146165 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing |