Submissions for variant NM_000059.4(BRCA2):c.1401G>C (p.Lys467Asn)

dbSNP: rs276174808

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000545323	SCV000635159	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-05-22	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 467 of the BRCA2 protein (p.Lys467Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 125944). 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 BRCA2 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587440	SCV000694536	uncertain significance	not provided	2016-11-21	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.1401G>C (p.Lys467Asn) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. One clinical diagnostic laboratory/reputable database classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color Diagnostics, LLC DBA Color Health	RCV001188331	SCV001355365	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001188331	SCV002699139	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-10	criteria provided, single submitter	clinical testing	The p.K467N variant (also known as c.1401G>C), located in coding exon 9 of the BRCA2 gene, results from a G to C substitution at nucleotide position 1401. The lysine at codon 467 is replaced by asparagine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington	RCV001188331	SCV003850061	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).
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112917	SCV000145866	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2010-12-17	no assertion criteria provided	clinical testing