Submissions for variant NM_000059.4(BRCA2):c.71del (p.Asp23_Leu24insTer)

dbSNP: rs397507903

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000241037	SCV000300290	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	RCV000166421	SCV000217216	pathogenic	Hereditary cancer-predisposing syndrome	2017-03-14	criteria provided, single submitter	clinical testing	The c.71delT pathogenic mutation (also known as 299delT or p.L24*), located in coding exon 2 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 71, causing a translational frameshift with a predicted alternate stop codon. This mutation has been reported in a French breast cancer family (Muller et al.BMC Medical Genetics2011; 12:121). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000241037	SCV000327608	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496358	SCV002189320	pathogenic	Hereditary breast ovarian cancer syndrome	2023-04-22	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: 52286). This variant is also known as 297delT. This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 9150172). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu24*) 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).
Baylor Genetics	RCV003473398	SCV004210354	pathogenic	Familial cancer of breast	2023-04-05	criteria provided, single submitter	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496358	SCV000587535	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research