Submissions for variant NM_000059.4(BRCA2):c.3859_3860del (p.Lys1286_Asn1287insTer)

dbSNP: rs80359406

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)	RCV000113228	SCV000300673	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.
Ambry Genetics	RCV000216461	SCV000278213	pathogenic	Hereditary cancer-predisposing syndrome	2024-04-04	criteria provided, single submitter	clinical testing	The c.3859_3860delAA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 3859 to 3860, causing a translational frameshift with a predicted alternate stop codon (p.N1287*). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Counsyl	RCV000113228	SCV000488437	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-03-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000216461	SCV000906905	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides 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 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	RCV000496958	SCV001586044	pathogenic	Hereditary breast ovarian cancer syndrome	2017-06-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 51543). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn1287*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113228	SCV000146314	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496958	SCV000587683	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research