ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.1724G>A (p.Ser575Asn)

gnomAD frequency: 0.00003  dbSNP: rs774352844
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220167 SCV000275091 likely benign Hereditary cancer-predisposing syndrome 2021-03-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000547252 SCV000632982 uncertain significance Familial cancer of breast 2025-02-02 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 575 of the BARD1 protein (p.Ser575Asn). This variant is present in population databases (rs774352844, gnomAD 0.01%). 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: 231290). 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. Experimental studies have shown that this missense change does not substantially affect BARD1 function (PMID: 30925164). 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.
Color Diagnostics, LLC DBA Color Health RCV000220167 SCV000908563 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781931 SCV000920361 uncertain significance not specified 2018-02-23 criteria provided, single submitter clinical testing Variant summary: BARD1 c.1724G>A (p.Ser575Asn) alters a conserved nucleotide resulting in a conservative amino acid change located in the BRCT domain (IPR001357) of 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 1.1e-05 in 277056 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BARD1 causing Hereditary Breast and Ovarian Cancer (1.1e-05 vs 0.00025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1724G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV001589147 SCV001815166 uncertain significance not provided 2023-05-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate homology-directed repair similar to wildtype (Adamovich et al., 2019); This variant is associated with the following publications: (PMID: 30925164, 17550235)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001589147 SCV002046725 uncertain significance not provided 2021-03-16 criteria provided, single submitter clinical testing
Baylor Genetics RCV000547252 SCV005054571 uncertain significance Familial cancer of breast 2024-03-11 criteria provided, single submitter clinical testing

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