ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3061A>G (p.Ser1021Gly)

dbSNP: rs2053648539
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284542 SCV001470383 uncertain significance not provided 2020-03-25 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV003158650 SCV003849152 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 RCV003158650 SCV005547486 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-15 criteria provided, single submitter clinical testing The p.S1021G variant (also known as c.3061A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3061. The serine at codon 1021 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005094333 SCV005732525 uncertain significance Hereditary breast ovarian cancer syndrome 2024-12-30 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1021 of the BRCA1 protein (p.Ser1021Gly). 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: 993203). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

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