ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1655G>A (p.Gly552Asp)

dbSNP: rs397508893
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777432 SCV000913294 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-05 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 552 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001856145 SCV002189576 uncertain significance Hereditary breast ovarian cancer syndrome 2021-06-19 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 631260). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 552 of the BRCA1 protein (p.Gly552Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
University of Washington Department of Laboratory Medicine, University of Washington RCV000777432 SCV003851144 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV000777432 SCV005100985 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-11 criteria provided, single submitter clinical testing The p.G552D variant (also known as c.1655G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1655. The glycine at codon 552 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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