Submissions for variant NM_000059.4(BRCA2):c.10095_10096insT (p.Ser3366Ter)

gnomAD frequency: 0.00033  dbSNP: rs730881599

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV004017655	SCV000605775	uncertain significance	not provided	2019-05-08	criteria provided, single submitter	clinical testing	The p.Ser3366X variant in BRCA2 has not been previously reported in individuals with cancer, but has been identified in 40/66644 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 3366. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. It is unclear if this will impact the protein function. In summary, the clinical significance of the p.Ser3366X variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000637965	SCV000759445	likely benign	Hereditary breast ovarian cancer syndrome	2024-05-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771138	SCV000902926	likely benign	Hereditary cancer-predisposing syndrome	2017-02-22	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196562	SCV001367170	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2020-02-10	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PVS1.
Sema4, Sema4	RCV000771138	SCV002533187	likely benign	Hereditary cancer-predisposing syndrome	2021-02-17	criteria provided, single submitter	curation
Ambry Genetics	RCV000771138	SCV002743211	likely benign	Hereditary cancer-predisposing syndrome	2020-12-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000637965	SCV002050308	uncertain significance	Hereditary breast ovarian cancer syndrome	2021-12-21	no assertion criteria provided	clinical testing