Submissions for variant NM_000059.4(BRCA2):c.-39-12_-39-10del

dbSNP: rs276174798

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478269	SCV000569168	likely benign	not specified	2018-02-27	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.
Color Diagnostics, LLC DBA Color Health	RCV000581005	SCV000683386	likely benign	Hereditary cancer-predisposing syndrome	2016-08-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000709284	SCV001010585	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-30	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798037	SCV002043014	uncertain significance	Breast and/or ovarian cancer	2020-04-24	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000031296	SCV002761800	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2020-04-27	criteria provided, single submitter	clinical testing	The BRCA2 c.-39-12_-39-10delTCT variant is classified as VUS (BS3)
Sharing Clinical Reports Project (SCRP)	RCV000031296	SCV000053901	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2010-12-17	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031296	SCV000145913	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354020	SCV000591648	uncertain significance	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRCA2, EXON02, c.-39-12_-39-10delTCT variant was not identified in the literature, but was identified in dbSNP (ID: rs276174798) “With non-pathogenic allele”, in UMD 2X as an “unclassified variant” (UV), and in the BIC database 7X as a variant with unknown clinical importance. This variant is located in the 3' splice region of the 5' UTR, which may be involved in splicing activity of Exon 2 (the first coding exon). The variant does not affect the invariant -1 and -2 positions; however, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) provide inconsistent predictions regarding splicing; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown significance.
PreventionGenetics, part of Exact Sciences	RCV004532430	SCV004747743	likely benign	BRCA2-related disorder	2019-07-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).