Submissions for variant NM_000059.4(BRCA2):c.10024G>T (p.Glu3342Ter)

dbSNP: rs28897761

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129731	SCV000184536	likely benign	Hereditary cancer-predisposing syndrome	2018-09-19	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.
Counsyl	RCV000112832	SCV000489129	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2016-08-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000422123	SCV000515387	likely benign	not specified	2017-08-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000422123	SCV000694488	likely benign	not specified	2021-10-21	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.10024G>T (p.Glu3342X) 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. This variant in the last exon of BRCA2 located in the extreme C terminus, removes the last 76 amino acids (amino acid total: 3418). Truncations downstream of this position have not been been classified as pathogenic by our laboratory. The variant was absent in 250966 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10024G>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. At-least one publication states that this variant was not identified as part of an affected breast cancer family and, because it occurs downstream of the Lys3326ter polymorphism, it is unlikely to be cancer associated (T. Frank, personal communication, cited in Spain_1999). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments but with a predominant consensus as likely benign (n=4) (VUS, n=2). Based on the evidence outlined above, the variant was classified as likely benign.
Color Diagnostics, LLC DBA Color Health	RCV000129731	SCV001350587	likely benign	Hereditary cancer-predisposing syndrome	2020-04-16	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588538	SCV001470187	uncertain significance	not provided	2019-10-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001483406	SCV001687797	likely benign	Hereditary breast ovarian cancer syndrome	2024-12-12	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112832	SCV000145743	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	1999-04-12	no assertion criteria provided	clinical testing