Submissions for variant NM_000059.4(BRCA2):c.2471del (p.Ala823_Leu824insTer)

dbSNP: rs886040427

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000256881	SCV000324079	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000256881	SCV000326709	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496820	SCV000827281	pathogenic	Hereditary breast ovarian cancer syndrome	2022-09-01	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: 266700). This variant is also known as 2699delT. A different variant (c.2471_2476delTAAATG) giving rise to the same protein effect has been determined to be pathogenic (PMID: 15858120). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu824*) 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).
Ambry Genetics	RCV001015666	SCV001176526	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-21	criteria provided, single submitter	clinical testing	The c.2471delT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 2471, causing a translational frameshift with a predicted alternate stop codon (p.L824*). This alteration has been identified in patients with ovarian cancer (Sakai W et al. Nature. 2008 Feb;451:1116-20; Walsh CS et al. Clin. Cancer Res. 2008 Dec;14:7645-51; Dhillon KK et al. Cancer Sci. 2011 Apr;102:663-9). Of note, this mutation is also designated as 2699delT in published literature. In addition to the clinical data presented in the literature, 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.
Baylor Genetics	RCV003475864	SCV004210532	pathogenic	Familial cancer of breast	2022-07-23	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477878	SCV004219544	pathogenic	not provided	2023-03-02	criteria provided, single submitter	clinical testing	This nonsense variant causes the premature termination of BRCA2 protein synthesis. It 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 ovarian cancer (PMID: 18264087 (2008), 19047089 (2008)). The variant has also been reported in a world-wide screen of BRCA1/BRCA2 families (PMID: 29446198 (2018)).Based on the available information, this variant is classified as pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV001015666	SCV004361262	pathogenic	Hereditary cancer-predisposing syndrome	2023-12-11	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 is also known as 2699delT in the literature. This variant has been reported in an individual affected with ovarian cancer (PMID: 18264087, 19047089). 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.
GeneDx	RCV003477878	SCV005372889	pathogenic	not provided	2024-04-05	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; Observed in individuals with BRCA2-related cancers (PMID: 18264087, 19047089); Not observed in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 2699delT; This variant is associated with the following publications: (PMID: 19047089, 18264087, 21205087, 29446198)
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496820	SCV000587634	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research