Submissions for variant NM_000059.4(BRCA2):c.4935del (p.Glu1646fs)

dbSNP: rs80359472

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113360	SCV000300800	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	RCV000113360	SCV000327105	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000113360	SCV000489494	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-10-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000581036	SCV000683661	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-23	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 11 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. This variant has been reported in 2 individuals affected with breast cancer (PMID: 17445839, Color internal data). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496709	SCV001578002	pathogenic	Hereditary breast ovarian cancer syndrome	2023-07-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1646Lysfs*24) 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 premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (HBOC) (PMID: 14985394). This variant is also known as 5163delA. ClinVar contains an entry for this variant (Variation ID: 51745). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113360	SCV000146509	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496709	SCV000587731	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research