ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5454C>T (p.Asp1818=)

dbSNP: rs1555574705
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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 RCV000579674 SCV000683318 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing This synonymous variant does not change the amino acid sequence of the BRCA1 protein. However, a different variant occurring in the same codon, c.5453A>G, results in skipping of exon 22 (BIC exon 23) and is known to be pathogenic (Clinvar variation ID: 37672), suggesting that an exonic splice enhancer may overlap with this codon (PMID 20875879). To our knowledge, functional studies have not been performed 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985442 SCV001133634 uncertain significance not provided 2018-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000579674 SCV001186098 likely benign Hereditary cancer-predisposing syndrome 2018-02-23 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.
Brotman Baty Institute, University of Washington RCV001077422 SCV001243353 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro
King Laboratory, University of Washington RCV001171389 SCV001251287 benign not specified 2019-09-01 no assertion criteria provided research

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