Submissions for variant NM_000059.4(BRCA2):c.7872T>G (p.Tyr2624Ter)

dbSNP: rs863224468

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000241341	SCV000301214	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000200163	SCV000253755	pathogenic	Hereditary breast ovarian cancer syndrome	2022-04-17	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: 216031). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr2624*) 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000200163	SCV002819504	likely pathogenic	Hereditary breast ovarian cancer syndrome	2022-12-13	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.7872T>G (p.Tyr2624X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251290 control chromosomes. To our knowledge, no occurrence of c.7872T>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV003456376	SCV004184309	pathogenic	not provided	2023-11-01	criteria provided, single submitter	clinical testing	BRCA2: PVS1, PM2