Submissions for variant NM_000465.4(BARD1):c.1513G>A (p.Gly505Arg)

dbSNP: rs864622240

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001565562	SCV001788930	uncertain significance	not provided	2019-09-12	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225859	SCV002505114	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Invitae	RCV002573195	SCV003487368	uncertain significance	Familial cancer of breast	2022-12-29	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1200514). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 505 of the BARD1 protein (p.Gly505Arg).
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV002573195	SCV004015223	uncertain significance	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with arginine at codon 505 of the BARD1 protein (p.Gly505Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This Variant not found in gnomAD genomes. This variant has not been reported in the literature in individuals with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 219764) with two submitters, both of which describe it as variant of uncertain significance. In-silico predictions show Pathogenic computational verdict based on 10 pathogenic predictions from BayesDel_addAF, DANN, EIGEN, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationAssessor, MutationTaster and SIFT vs 2 benign predictions from DEOGEN2 and PrimateAI. No functional studies have been published for this variant. Therefore, it has been classified as a Variant of Uncertain Significance.