Submissions for variant NM_007294.4(BRCA1):c.2213_2214dup (p.Lys739fs)

dbSNP: rs80357574

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031038	SCV000323426	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-10-18	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000167068	SCV000217896	pathogenic	Hereditary cancer-predisposing syndrome	2024-07-08	criteria provided, single submitter	clinical testing	The c.2213_2214dupTT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of TT at nucleotide position 2213, causing a translational frameshift with a predicted alternate stop codon (p.K739Lfs*15). This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. In addition, this variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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	RCV000031038	SCV000325294	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000657536	SCV000779272	pathogenic	not provided	2022-11-10	criteria provided, single submitter	clinical testing	Frameshift 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; Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 2332_2333dupTT
Labcorp Genetics (formerly Invitae), Labcorp	RCV001048511	SCV001212522	pathogenic	Hereditary breast ovarian cancer syndrome	2024-08-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys739Leufs*15) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 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: 29446198). ClinVar contains an entry for this variant (Variation ID: 37457). For these reasons, this variant has been classified as Pathogenic.
Sema4, Sema4	RCV000167068	SCV002538102	pathogenic	Hereditary cancer-predisposing syndrome	2022-01-23	criteria provided, single submitter	curation
Baylor Genetics	RCV000031038	SCV004211745	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-08-06	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005357168	SCV005914247	pathogenic	Fanconi anemia, complementation group S	2021-11-23	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031038	SCV000053632	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-10	no assertion criteria provided	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000031038	SCV003927167	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-05	no assertion criteria provided	clinical testing	A pathogenic frameshift mutation in the BRCA1 gene (p.Lys739fs) in this specimen. Pathogenic mutations in the BRCA1 gene cause Hereditary Breast/Ovarian Cancer syndrome (HBOC).