ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2175dup (p.Val726fs)

dbSNP: rs276174819
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Total submissions: 8
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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) RCV000031357 SCV000300495 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.
Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University RCV000240717 SCV000265904 pathogenic Breast neoplasm 2015-11-01 criteria provided, single submitter research
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031357 SCV000326665 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000637500 SCV000758961 pathogenic Hereditary breast ovarian cancer syndrome 2024-04-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val726Serfs*25) 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). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 22977638). This variant is also known as 2403insA. ClinVar contains an entry for this variant (Variation ID: 37776). For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000031357 SCV000883075 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2018-11-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV004018692 SCV005024980 pathogenic Hereditary cancer-predisposing syndrome 2024-01-10 criteria provided, single submitter clinical testing The c.2175dupA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of A at nucleotide position 2175, causing a translational frameshift with a predicted alternate stop codon (p.V726Sfs*25). This variant was reported in multiple individuals with features consistent with BRCA2-related hereditary breast and ovarian cancer syndrome (DE Silva S et al. Exp Ther Med, 2011 Nov;2:1163-1170; Schwartz M et al. Clin Genet, 2019 Dec;96:579-584). 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.
Sharing Clinical Reports Project (SCRP) RCV000031357 SCV000053962 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2006-06-19 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031357 SCV000146013 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2010-10-28 no assertion criteria provided clinical testing

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