ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7643_7644del (p.His2548fs)

dbSNP: rs886040724
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000256731 SCV000324574 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-10-18 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 RCV000256731 SCV000327701 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000480575 SCV000567866 pathogenic not provided 2022-08-29 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 at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 7871_7872delAT, 7871delAT, and c.7643delAT; Observed in an individual with breast cancer (Abulkhair et al., 2018); This variant is associated with the following publications: (PMID: 30199306)
Labcorp Genetics (formerly Invitae), Labcorp RCV001388725 SCV001589801 pathogenic Hereditary breast ovarian cancer syndrome 2023-01-03 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 30199306). This sequence change creates a premature translational stop signal (p.His2548Leufs*5) 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). ClinVar contains an entry for this variant (Variation ID: 267028). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002392788 SCV002670698 pathogenic Hereditary cancer-predisposing syndrome 2024-07-12 criteria provided, single submitter clinical testing The c.7643_7644delAT pathogenic mutation, located in coding exon 15 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 7643 to 7644, causing a translational frameshift with a predicted alternate stop codon (p.H2548Lfs*5). This variant was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620) and in a Saudi woman diagnosed with breast cancer under the age of 45 (Abulkhair O et al. J Glob Oncol, 2018 08;4:1-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 RCV004567816 SCV005059152 pathogenic Familial cancer of breast 2023-12-14 criteria provided, single submitter clinical testing

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