Submissions for variant NM_000059.4(BRCA2):c.5217_5218delinsC (p.Tyr1739_Leu1740insTer)

dbSNP: rs886040579

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001804316	SCV002052334	pathogenic	Hereditary cancer-predisposing syndrome	2020-12-09	criteria provided, single submitter	clinical testing	This variant deletes 2 and inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. A similar variant with a different nucleotide change but the same premature stop signal (ClinVar ID: 800652) has been reported in an individual with breast cancer (PMID: 31060517). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV001804316	SCV002640593	pathogenic	Hereditary cancer-predisposing syndrome	2020-09-11	criteria provided, single submitter	clinical testing	The c.5217_5218delTTinsC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.L1740*). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.