Submissions for variant NM_000059.4(BRCA2):c.5110_5113del (p.Glu1703_Arg1704insTer)

dbSNP: rs879254123

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)	RCV000257060	SCV000324297	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-10-18	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000235563	SCV000293579	pathogenic	not provided	2020-06-10	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Observed in individuals with breast and other cancers (Schrader 2016, Fostira 2020); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.5338_5341delAGAA; This variant is associated with the following publications: (PMID: 30720243, 26556299, 31209999, 31300551)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000257060	SCV000327131	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000457247	SCV000549606	pathogenic	Hereditary breast ovarian cancer syndrome	2021-07-29	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 affected with thyroid carcinoma (PMID: 26556299). ClinVar contains an entry for this variant (Variation ID: 246151). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg1704*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
Counsyl	RCV000257060	SCV000677844	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2017-01-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776493	SCV000912075	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 4 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 been identified in 2/231206 chromosomes 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.
Ambry Genetics	RCV000776493	SCV001185464	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-28	criteria provided, single submitter	clinical testing	The c.5110_5113delAGAA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 5110 to 5113, causing a translational frameshift with a predicted alternate stop codon (p.R1704*). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000235563	SCV002774328	pathogenic	not provided	2021-06-16	criteria provided, single submitter	clinical testing	This frameshift variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in individuals affected with different forms of cancer in the published literature (PMID: 26556299 (2016), 33807840 (2021)). Based on the available information, this variant is classified as pathogenic.