Submissions for variant NM_000059.4(BRCA2):c.386del (p.Asp129fs)

dbSNP: rs2072334992

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001048540	SCV001212552	pathogenic	Hereditary breast ovarian cancer syndrome	2019-11-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp129Valfs*7) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
Color Diagnostics, LLC DBA Color Health	RCV001190385	SCV001357848	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-18	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 4 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.