Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001315816 | SCV001506408 | uncertain significance | Familial cancer of breast | 2022-03-08 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects BARD1 function (PMID: 26350354). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1016763). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 34 of the BARD1 protein (p.Trp34Arg). |
Ambry Genetics | RCV002438710 | SCV002751202 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-16 | criteria provided, single submitter | clinical testing | The p.W34R variant (also known as c.100T>C), located in coding exon 1 of the BARD1 gene, results from a T to C substitution at nucleotide position 100. The tryptophan at codon 34 is replaced by arginine, an amino acid with dissimilar properties. Functional analyses demonstrates that this variant retains 40% homology-directed repair function compared to wild-type (Lee C et al. Hum. Mutat. 2015 Dec;36(12):1205-14). 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. |
KCCC/NGS Laboratory, |
RCV001315816 | SCV003936827 | uncertain significance | Familial cancer of breast | 2023-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces Tryptophan with Arginine at codon 34 of the BARD1 protein (p.Trp34Arg) an amino acid with dissimilar properties.The p.W34R variant (also known as c.100T>C), located in coding exon 1 of the BARD1 gene, results from a T to C substitution at nucleotide position 100. Functional analyses demonstrates that this variant retains 40% homology-directed repair function compared to wild-type (PMID: 26350354) . This amino acid position is not highly conserved (PhyloP100way =2.5) . In addition, the In-silico predictions show pathogenic computational verdict based on 10 pathogenic predictions from BayesDel addAF , MetaLR , MetaSVM , LRT , M-CAP , MVP , PrimateAI , PROVEAN , SIFT and polyphen vs 4 benign prediction from FATHMM , LIST-S2 , Mutation assessor and MutPred. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. Therefore, it has been classified as a Variant of Uncertain Significance. |