Submissions for variant NM_000059.4(BRCA2):c.3205_3206insTAATTGCAGTCAATTAATA (p.Ser1069delinsLeuIleAlaValAsnTer)

dbSNP: rs1064795469

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481346	SCV000571304	pathogenic	not provided	2017-03-01	criteria provided, single submitter	clinical testing	This insertion of 19 nucleotides in BRCA2 is denoted c.3205_3206ins19 at the cDNA level and p.Ser1069LeufsX6 (S1069LfsX6) at the protein level. The surrounding sequence is GTAT[ins19]CTGC. The insertion causes a frameshift which changes a Serine to a Leucine at codon 1069, and creates a premature stop codon at position 6 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Myriad Genetics, Inc.	RCV003335368	SCV004043141	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2023-05-12	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090957	SCV005754250	pathogenic	Hereditary breast ovarian cancer syndrome	2024-05-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1069Leufs*6) 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 variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 421956). For these reasons, this variant has been classified as Pathogenic.