Submissions for variant NM_000059.4(BRCA2):c.2672dup (p.Phe892fs)

dbSNP: rs2072462600

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001177012	SCV001341117	pathogenic	Hereditary cancer-predisposing syndrome	2021-01-04	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 11 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.
Invitae	RCV001218728	SCV001390624	pathogenic	Hereditary breast ovarian cancer syndrome	2021-10-20	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 29371908). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe892Leufs*5) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV001218728	SCV001424024	likely pathogenic	Hereditary breast ovarian cancer syndrome	2018-12-20	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide duplication in exon 11/28 of the BRCA2 gene that results in a frameshifted product with an early termination codon 5 amino acids downstream of the duplication at Phe892. This variant is predicted to generate a non-functional allele through either the expression of a truncated protein or a loss of BRCA2 expression due to nonsense-mediated decay. This variant is absent from the control population database gnomAD (0/232918 alleles). The variant has been observed and reported in a published research study as a pathogenic familial breast cancer variant (PMID: 29371908). Based upon the evidence, we consider this variant to be likely pathogenic.