Submissions for variant NM_000059.4(BRCA2):c.3458del (p.Lys1153fs)

dbSNP: rs80359386

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)	RCV000113182	SCV000300637	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113182	SCV000326869	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567473	SCV000666169	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-01	criteria provided, single submitter	clinical testing	The c.3458delA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 3458, causing a translational frameshift with a predicted alternate stop codon (p.K1153Rfs*15). In one study, this mutation was detected in 1/207 ovarian cancer patients who were offered BRCA1/2 testing, and the proband carrying this mutation also had a mother with ovarian cancer (George A et al. Sci Rep, 2016 Jul;6:29506). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496266	SCV000932073	pathogenic	Hereditary breast ovarian cancer syndrome	2023-05-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys1153Argfs*15) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 126014). This variant is also known as 3686delA. This premature translational stop signal has been observed in individual(s) with BRCA2-related conditions (PMID: 10923033, 21520333). This variant is not present in population databases (gnomAD no frequency).
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113182	SCV000146241	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496266	SCV000587672	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research