Submissions for variant NM_007294.4(BRCA1):c.3283A>G (p.Lys1095Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002445779	SCV002611534	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-07	criteria provided, single submitter	clinical testing	The p.K1095E variant (also known as c.3283A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3283. The lysine at codon 1095 is replaced by glutamic acid, an amino acid with similar properties. This alteration was observed with an allele frequency of 0.00071 in 7,051 unselected female breast cancer patients and was not observed in 11,241 female controls of Japanese ancestry. In addition, it was not observed in unselected male breast cancer patients and was observed with an allele frequency of 0.0001 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). In another case-control study, this alteration was reported with a carrier frequency of 0.00013 in 7636 unselected prostate cancer patients and 0.00008 in 12366 male controls of Japanese ancestry (Momozawa Y. J Natl Cancer Inst. 2020 Apr;112(4):369-376). This amino acid position is poorly 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	RCV002445779	SCV003847158	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).