Submissions for variant NM_007294.4(BRCA1):c.3155A>G (p.Asn1052Ser)

gnomAD frequency: 0.00001  dbSNP: rs398122672

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Molecular Medicine, Queen's University	RCV000496718	SCV000588043	uncertain significance	not specified	2017-04-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579719	SCV000683089	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-15	criteria provided, single submitter	clinical testing
Invitae	RCV000691894	SCV000819692	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1052 of the BRCA1 protein (p.Asn1052Ser). 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: 91606). 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 with a negative predictive value of 95%. 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	RCV000579719	SCV001180127	uncertain significance	Hereditary cancer-predisposing syndrome	2021-05-06	criteria provided, single submitter	clinical testing	The p.N1052S variant (also known as c.3155A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3155. The asparagine at codon 1052 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000496718	SCV002050795	uncertain significance	not specified	2021-12-06	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000579719	SCV003847288	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).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477479	SCV004219339	uncertain significance	not provided	2023-05-04	criteria provided, single submitter	clinical testing	This variant has not been reported in the published literature in individuals with BRCA1-related cancers. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Sharing Clinical Reports Project (SCRP)	RCV000077123	SCV000108920	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2013-05-29	no assertion criteria provided	clinical testing