Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219067 | SCV000273545 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-10 | criteria provided, single submitter | clinical testing | The p.E652G variant (also known as c.1955A>G), located in coding exon 10 of the BARD1 gene, results from an A to G substitution at nucleotide position 1955. The glutamic acid at codon 652 is replaced by glycine, an amino acid with similar properties. In one study, this alteration was observed in 0/3236 cases with invasive epithelial ovarian cancer and 1/3431 controls (Ramus SJ et al. J Natl Cancer Inst, 2015 Nov;107:). This alteration was also reported in a study of 1297 cases of early-onset breast cancer and 1121 controls (Young EL et al. J. Med. Genet. 2016 06;53:366-76). This amino acid position is highly 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. |
| Labcorp Genetics |
RCV000233938 | SCV000284935 | uncertain significance | Familial cancer of breast | 2023-09-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 652 of the BARD1 protein (p.Glu652Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 26787654). ClinVar contains an entry for this variant (Variation ID: 230114). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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, |
RCV000219067 | SCV000682743 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-30 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 652 of the BARD1 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. |
| Mendelics | RCV002247647 | SCV002517918 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000233938 | SCV004217253 | uncertain significance | Familial cancer of breast | 2024-03-18 | criteria provided, single submitter | clinical testing |