Submissions for variant NM_000059.4(BRCA2):c.6644dup (p.Tyr2215Ter)

dbSNP: rs80359615

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)	RCV000113619	SCV000301083	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000113619	SCV000296584	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-12-08	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113619	SCV000327484	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496577	SCV001592618	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr2215*) 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 breast and/or ovarian cancer (PMID: 9667259, 26976419). This variant is also known as 6872insA. ClinVar contains an entry for this variant (Variation ID: 52146). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002362673	SCV002662206	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-17	criteria provided, single submitter	clinical testing	The c.6644dupA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of A at nucleotide position 6644, causing a translational frameshift with a predicted alternate stop codon (p.Y2215*). This mutation has been detected in multiple breast and/or ovarian cancer cohorts (Frank TS et al. J Clin Oncol, 1998 Jul;16:2417-25; Tung N et al. J Clin Oncol, 2016 May;34:1460-8; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620), as well as an individual with prostate cancer (Pilié PG et al. Cancer, 2017 Oct;123:3925-3932). Of note, this alteration is also designated as 6872insA in the 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	RCV003473385	SCV004212910	pathogenic	Familial cancer of breast	2021-09-07	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113619	SCV000146899	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496577	SCV000587862	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research