Submissions for variant NM_000465.4(BARD1):c.157T>G (p.Cys53Gly)

dbSNP: rs1354779388

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001776483	SCV002013089	uncertain significance	not provided	2021-03-29	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV002544211	SCV003268021	uncertain significance	Familial cancer of breast	2023-10-28	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 53 of the BARD1 protein (p.Cys53Gly). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1320504). 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. Studies have shown that this missense change results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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.
Baylor Genetics	RCV002544211	SCV004217298	uncertain significance	Familial cancer of breast	2023-03-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492270	SCV004239858	uncertain significance	Breast and/or ovarian cancer	2022-09-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004040773	SCV005035598	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-16	criteria provided, single submitter	clinical testing	The p.C53G variant (also known as c.157T>G), located in coding exon 1 of the BARD1 gene, results from a T to G substitution at nucleotide position 157. The cysteine at codon 53 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.