Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000709327 | SCV000838841 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000113604 | SCV001139152 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000709327 | SCV001555865 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-12-11 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 52123). 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. 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. This missense change has been observed in individual(s) with BRCA2-related disease (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2178 of the BRCA2 protein (p.His2178Asn). |
University of Washington Department of Laboratory Medicine, |
RCV003157314 | SCV003847246 | 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). |
Ambry Genetics | RCV003157314 | SCV003855516 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.H2178N variant (also known as c.6532C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 6532. The histidine at codon 2178 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Color Diagnostics, |
RCV003157314 | SCV004362168 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with asparagine at codon 2178 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 not been reported in individuals affected with hereditary cancer in the literature. 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 |
RCV000113604 | SCV000146877 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Department of Medical and Surgical Sciences, |
RCV000113604 | SCV004228428 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-09-01 | no assertion criteria provided | clinical testing | PM2(Supporting)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042) |