Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031043 | SCV000299742 | 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 | RCV000132306 | SCV000187392 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | The c.2299delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2299, causing a translational frameshift with a predicted alternate stop codon (p.S767Afs*25). This mutation has been reported in multiple individuals with a personal and/or family history consistent with Hereditary Breast and Ovarian Cancer syndrome (HBOC) (Tworek H et al. Cancer Genet. Cytogenet. 1999 Jul;112:105-18; Fetzer S et al. Cancer Genet. Cytogenet. 1999 Aug;113:58-64; Ramus SJ et al. Hum. Mutat. 2007 Dec;28:1207-15; Zhang J et al. Breast Cancer Res. Treat. 2012 Apr;132:421-8; Lynce F et al. Breast Cancer Res. Treat. 2015 Aug;153:201-9; Bhaskaran SP et al. Int. J. Cancer. 2019 Jan). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000031043 | SCV000325317 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000481946 | SCV000568419 | pathogenic | not provided | 2023-10-03 | 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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2418delA; This variant is associated with the following publications: (PMID: 26187060, 10459348, 10686936, 12491487, 17688236, 21614564, 26250392, 21702907, 26269718, 28152038, 16267036, 30702160, 20104584, 29446198, 35535697, 31825140) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587984 | SCV000698936 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-11-24 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.2299delA (p.Ser767AlafsX25) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251084 control chromosomes (gnomAD). c.2299delA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer Syndrome. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five other submitters, including an expert panel (ENIGMA), have provided clinical-significance assessments for this variant in ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000587984 | SCV000944014 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser767Alafs*25) 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 ovarian cancer and breast cancer (PMID: 10686936, 26187060). This variant is also known as 2418delA. ClinVar contains an entry for this variant (Variation ID: 37462). For these reasons, this variant has been classified as Pathogenic. |
Laan Lab, |
RCV000031043 | SCV002538615 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2021-05-01 | criteria provided, single submitter | research | |
Baylor Genetics | RCV000031043 | SCV004216904 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-09-28 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000481946 | SCV004222596 | pathogenic | not provided | 2022-12-06 | criteria provided, single submitter | clinical testing | This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with breast cancer (PMID: 26250392 (2015), 21614564 (2012), 12491487 (2003)), and in individuals with ovarian cancer (PMID: 10686936 (1999), 10459348 (1999)). Based on the available information, this variant is classified as pathogenic. |
Sharing Clinical Reports Project |
RCV000031043 | SCV000053637 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-03-10 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031043 | SCV000144372 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing |