Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000222624 | SCV000274279 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-03-02 | criteria provided, single submitter | clinical testing | The p.S704G variant (also known as c.2110A>G), located in coding exon 11 of the BARD1 gene, results from an A to G substitution at nucleotide position 2110. The serine at codon 704 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 40000 alleles tested) in our clinical cohort. 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 p.S704G remains unclear. |
Labcorp Genetics |
RCV000535249 | SCV000633007 | uncertain significance | Familial cancer of breast | 2023-04-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 230654). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 704 of the BARD1 protein (p.Ser704Gly). |
Color Diagnostics, |
RCV000222624 | SCV001733843 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-03 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with glycine at codon 704 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. |
Baylor Genetics | RCV000535249 | SCV004217276 | uncertain significance | Familial cancer of breast | 2023-05-05 | criteria provided, single submitter | clinical testing |