Submissions for variant NM_000059.4(BRCA2):c.9096_9097del (p.Lys3032fs)

dbSNP: rs397507419

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001018830	SCV001180111	pathogenic	Hereditary cancer-predisposing syndrome	2023-10-03	criteria provided, single submitter	clinical testing	The c.9096_9097delAA pathogenic mutation, located in coding exon 22 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 9096 to 9097, causing a translational frameshift with a predicted alternate stop codon (p.K3032Nfs*11). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Color Diagnostics, LLC DBA Color Health	RCV001018830	SCV001348140	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 23 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193953	SCV001363146	likely pathogenic	Hereditary breast ovarian cancer syndrome	2019-08-16	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.9096_9097delAA (p.Lys3032AsnfsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245952 control chromosomes (gnomAD). To our knowledge, no occurrence of c.9096_9097delAA in individuals affected with Hereditary Breast and Ovarian Cancer 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 likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001193953	SCV001585727	pathogenic	Hereditary breast ovarian cancer syndrome	2024-05-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys3032Asnfs*11) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29383094). ClinVar contains an entry for this variant (Variation ID: 823004). For these reasons, this variant has been classified as Pathogenic.