ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2043dup (p.Asn682Ter)

dbSNP: rs863224510
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Total submissions: 7
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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) RCV000238610 SCV000299689 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000198736 SCV000253906 pathogenic Hereditary breast ovarian cancer syndrome 2021-11-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn682*) 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 BRCA1-related conditions (PMID: 22762150). ClinVar contains an entry for this variant (Variation ID: 216102). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281711 SCV000296434 pathogenic not provided 2020-04-02 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000238610 SCV000325218 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000572957 SCV000661093 pathogenic Hereditary cancer-predisposing syndrome 2017-11-29 criteria provided, single submitter clinical testing The c.2043dupT pathogenic mutation (also known as p.N682*), located in coding exon 9 of the BRCA1 gene, results from a duplication of T at nucleotide position 2043. This changes the amino acid from a asparagine to a stop codon within coding exon 9. 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.
Counsyl RCV000238610 SCV000677721 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2017-03-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000572957 SCV001348871 pathogenic Hereditary cancer-predisposing syndrome 2019-11-18 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known as c.787+1256dup by an alternative transcript (NM_007298.3). This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in a hereditary breast and ovarian cancer family (PMID: 22762150). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.

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