ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.54C>G (p.Asn18Lys)

gnomAD frequency: 0.00001  dbSNP: rs587780032
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766538 SCV000149545 uncertain significance not provided 2024-10-22 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31036035)
Ambry Genetics RCV000115636 SCV000184256 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-05 criteria provided, single submitter clinical testing The p.N18K variant (also known as c.54C>G), located in coding exon 1 of the BARD1 gene, results from a C to G substitution at nucleotide position 54. The asparagine at codon 18 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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 this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000766538 SCV000600199 uncertain significance not provided 2023-07-13 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in individuals with BARD1-related conditions in the published literature. The frequency of this variant in the general population, 0.00022 (4/17842 chromosomes in East Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000535960 SCV000633044 uncertain significance Familial cancer of breast 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 18 of the BARD1 protein (p.Asn18Lys). This variant is present in population databases (rs587780032, gnomAD 0.02%). 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: 127740). 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.
Counsyl RCV000535960 SCV000786449 uncertain significance Familial cancer of breast 2018-05-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000535960 SCV000896923 uncertain significance Familial cancer of breast 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000115636 SCV000903479 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-25 criteria provided, single submitter clinical testing This missense variant replaces asparagine with lysine at codon 18 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 but has been reported in an unaffected individual in a breast cancer case-control study (PMID: 31036035). This variant has been identified in 4/246038 chromosomes 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001731379 SCV001983475 uncertain significance not specified 2021-09-04 criteria provided, single submitter clinical testing Variant summary: BARD1 c.54C>G (p.Asn18Lys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 214678 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.54C>G in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000766538 SCV002009138 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153370 SCV003843300 benign Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000535960 SCV004019258 likely benign Familial cancer of breast 2023-02-24 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Baylor Genetics RCV000535960 SCV005054572 uncertain significance Familial cancer of breast 2024-03-08 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003935101 SCV004761773 uncertain significance BARD1-related disorder 2024-02-05 no assertion criteria provided clinical testing The BARD1 c.54C>G variant is predicted to result in the amino acid substitution p.Asn18Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD and is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127740/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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