Submissions for variant NM_000059.4(BRCA2):c.2656A>C (p.Asn886His)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003226873	SCV003923238	uncertain significance	not specified	2023-03-07	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.2656A>C (p.Asn886His) results in a conservative amino acid change located in the NPM1-interacting region (UniProt) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.3e-06 in 231126 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2656A>C in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV004285613	SCV005024898	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-11	criteria provided, single submitter	clinical testing	The p.N886H variant (also known as c.2656A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 2656. The asparagine at codon 886 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.