ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2762del (p.Gln921fs)

dbSNP: rs80357703
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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) RCV000111934 SCV000299830 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.
Ambry Genetics RCV000165693 SCV000216432 pathogenic Hereditary cancer-predisposing syndrome 2014-08-29 criteria provided, single submitter clinical testing The c.2762delA pathogenic mutation (also known as 2881delA), located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2762, causing a translational frameshift with a predicted alternate stop codon. This alteration has been reported in multiple breast and/or ovarian cancer families of Czech ancestry (Machackova E, BMC Cancer 2008 ; 8:140). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111934 SCV000325458 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000657211 SCV000778937 pathogenic not provided 2022-03-17 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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Foretova 2004, Machackova 2008); 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 2881delA; This variant is associated with the following publications: (PMID: 18489799, 15024741, 32295079, 29446198, 31409081, 20104584, 32438681)
Labcorp Genetics (formerly Invitae), Labcorp RCV001383398 SCV001582531 pathogenic Hereditary breast ovarian cancer syndrome 2023-01-01 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 15024741, 18489799, 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln921Argfs*79) 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). ClinVar contains an entry for this variant (Variation ID: 54674). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000165693 SCV004360255 pathogenic Hereditary cancer-predisposing syndrome 2021-10-25 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least one individual and a family affected with breast or ovarian cancer and has been identified in a family among the CIMBA participants (PMID: 15024741, 18489799, 29446198). 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111934 SCV000144538 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2005-07-20 no assertion criteria provided clinical testing
CZECANCA consortium RCV001271010 SCV001451822 pathogenic Breast and/or ovarian cancer 2019-06-11 no assertion criteria provided clinical testing

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