Submissions for variant NM_000059.4(BRCA2):c.7846del (p.Ser2616fs)

dbSNP: rs397507940

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)	RCV000162059	SCV000301207	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	RCV000162059	SCV000327744	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000522847	SCV000617473	pathogenic	not provided	2017-03-13	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA2 is denoted c.7846delT at the cDNA level and p.Ser2616LeufsX32 (S2616LfsX32) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 8074delT. The normal sequence, with the base that is deleted in brackets, is TATT[delT]CTAG. The deletion causes a frameshift which changes a Serine to a Leucine at codon 2616, and creates a premature stop codon at position 32 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.7846delT has been observed in individuals with hereditary breast and/or ovarian cancer (Meindl 2002, Tea 2014). We consider this variant to be pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000773101	SCV000906562	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 17 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 individuals with personal and/or family history of breast and/or ovarian cancer (PMID: 11802209, 2377269). 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	RCV000496617	SCV003442138	pathogenic	Hereditary breast ovarian cancer syndrome	2022-06-26	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: 52425). This variant is also known as 8074delT and/or 2647X. This premature translational stop signal has been observed in individual(s) with personal and/or family history of breast and/or ovarian cancer (PMID: 11802209, 24156927). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser2616Leufs*32) 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).
Revvity Omics, Revvity	RCV000522847	SCV003821900	likely pathogenic	not provided	2022-09-26	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Medical University Innsbruck	RCV000162059	SCV000212028	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-02-11	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496617	SCV000587914	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research