ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.566A>G (p.Asp189Gly)

dbSNP: rs1555594067
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000583245 SCV000688645 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-17 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 189 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000794776 SCV000934206 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 189 of the BRCA1 protein (p.Asp189Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 491179). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. 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.
Ambry Genetics RCV000583245 SCV001186393 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-13 criteria provided, single submitter clinical testing The p.D189G variant (also known as c.566A>G), located in coding exon 7 of the BRCA1 gene, results from an A to G substitution at nucleotide position 566. The aspartic acid at codon 189 is replaced by glycine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004802265 SCV004818434 uncertain significance BRCA1-related cancer predisposition 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 189 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant is reported as functional in a high-throughput homology-mediated DNA repair assay (PMID: 30219179). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
Fulgent Genetics, Fulgent Genetics RCV005019007 SCV005640300 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2024-06-04 criteria provided, single submitter clinical testing

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