Submissions for variant NM_000059.4(BRCA2):c.610dup (p.Leu204fs)

dbSNP: rs80359560

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000698847	SCV000827536	pathogenic	Hereditary breast ovarian cancer syndrome	2024-08-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu204Profs*2) 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: 576367). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985558	SCV001133852	likely pathogenic	not provided	2023-01-30	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the BRCA2 mRNA and is predicted to cause the premature termination of BRCA2 protein synthesis. The variant has not been reported in individuals with BRCA2-related diseases in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic.
Ambry Genetics	RCV002352175	SCV002660012	pathogenic	Hereditary cancer-predisposing syndrome	2023-08-31	criteria provided, single submitter	clinical testing	The c.610dupC pathogenic mutation, located in coding exon 6 of the BRCA2 gene, results from a duplication of C at nucleotide position 610, causing a translational frameshift with a predicted alternate stop codon (p.L204Pfs*2). 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.
Fulgent Genetics, Fulgent Genetics	RCV002477596	SCV002797203	pathogenic	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3	2022-04-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV002352175	SCV004361182	pathogenic	Hereditary cancer-predisposing syndrome	2023-06-20	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 7 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 BRCA2-related disorders 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.