ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2990A>G (p.Asn997Ser)

dbSNP: rs1597866298
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001017808 SCV001178959 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-25 criteria provided, single submitter clinical testing The p.N997S variant (also known as c.2990A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 2990. The asparagine at codon 997 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001228594 SCV001400999 uncertain significance Hereditary breast ovarian cancer syndrome 2019-09-26 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 997 of the BRCA1 protein (p.Asn997Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency).
University of Washington Department of Laboratory Medicine, University of Washington RCV001017808 SCV003849206 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).

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