Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000696962 | SCV000825547 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 3037 of the BRCA2 protein (p.Gln3037His). This variant is present in population databases (rs200814465, gnomAD 0.0009%). 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: 252856). 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. |
| Color Diagnostics, |
RCV001191885 | SCV001359809 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-18 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with histidine at codon 3037 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 been identified in 1/248824 chromosomes 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001283946 | SCV001469464 | uncertain significance | not provided | 2019-09-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001191885 | SCV002684758 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.Q3037H variant (also known as c.9111A>T), located in coding exon 22 of the BRCA2 gene, results from an A to T substitution at nucleotide position 9111. The glutamine at codon 3037 is replaced by histidine, 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. |
| Sharing Clinical Reports Project |
RCV000239094 | SCV000297459 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2014-01-24 | no assertion criteria provided | clinical testing |