Submissions for variant NM_000059.4(BRCA2):c.9481A>T (p.Lys3161Ter)

dbSNP: rs80359222

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000114117	SCV000301397	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000114117	SCV000328142	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center	RCV000414553	SCV000492447	pathogenic	Breast neoplasm		criteria provided, single submitter	research
Invitae	RCV000496504	SCV001589949	pathogenic	Hereditary breast ovarian cancer syndrome	2023-05-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 52848). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 24884479, 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys3161*) 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).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003476939	SCV004220659	pathogenic	not provided	2022-09-06	criteria provided, single submitter	clinical testing	This nonsense variant causes the premature termination of BRCA2 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with breast cancer (PMID: 24884479 (2014)) and in individuals from a large breast cancer association study (PMID: 29446198 (2018)). Based on the available information, this variant is classified as pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV003584525	SCV004362820	pathogenic	Hereditary cancer-predisposing syndrome	2022-09-26	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 25 of the BRCA2 gene, creating a premature translation stop signal. This variant is also known in the literature as 9709A>T. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast cancer, including 1 male individual (PMID: 24884479, 34072659, 34100114), and has been identified in 8 families among the CIMBA participants (PMID: 29446198). 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.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114117	SCV000147648	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	1999-06-22	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496504	SCV000588008	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research