Submissions for variant NM_000059.4(BRCA2):c.3604A>G (p.Lys1202Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002455250	SCV002617415	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-28	criteria provided, single submitter	clinical testing	The p.K1202E variant (also known as c.3604A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 3604. The lysine at codon 1202 is replaced by glutamic acid, an amino acid with similar properties. This alteration was not observed in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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	RCV002455250	SCV003846732	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).