ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5078_5080del (p.Ala1693del) (rs80358345)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166817 SCV000217631 likely pathogenic Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing The c.5078_5080delCTG variant (also known as p.A1693del) is located in coding exon 16 of the BRCA1 gene. This variant results from an in-frame deletion of 3 nucleotides at positions 5078 to 5080, which would be expected to cause the removal of a well-conserved alanine residue at codon 1693. This alteration (also designated as 5196del3 and 5197_5199del3) occurs near the native splice acceptor site, and reverse transcription of RNA isolated from carriers has demonstrated aberrant splicing and an in-frame deletion of 26 amino acids in the functionally important BRCT domain (Campos, B et al. Hum Mutat. 2003 Oct;22(4):337; Houdayer, C et al. Hum Mutat. 2012 Aug;33(8):1228-38). In addition, this alteration was identified in a Spanish breast and ovarian cancer family (Diez, O et al. Hum Mutat. 2003 Oct;22(4):301-12). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
GeneDx RCV000237025 SCV000293461 likely pathogenic not provided 2016-02-12 criteria provided, single submitter clinical testing This in-frame deletion of 3 nucleotides in BRCA1 is denoted c.5078_5080delCTG at the cDNA level and p.Ala1693del (A1693del) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 c.5197_5199delCTG. The normal sequence, with the bases that are deleted in braces, is GATG[CTG]AGTT. This deletion of a single Alanine residue occurs at a position that is not conserved across species and is located in the BRCT 1 domain and a region known to interact with multiple proteins (Narod 2004, Paul 2014). This variant was observed in a breast/ovarian cancer family and was shown in splicing assays to result in skipping of exon 18 in both cDNA and RNA (Díez 2003, Houdayer 2012, Campos 2003). We consider this deletion to be likely pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083215 SCV000326150 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Genologica Medica RCV000083215 SCV000577933 likely pathogenic Breast-ovarian cancer, familial 1 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001379223 SCV001576984 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-08-26 criteria provided, single submitter clinical testing This variant, c.5078_5080del, results in the deletion of 1 amino acid(s) of the BRCA1 protein (p.Ala1693del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several families affected with breast and/or ovarian cancer (PMID: 12955716, 29884136, 29446198). This variant is also known as 5197_5199del3 in the literature. ClinVar contains an entry for this variant (Variation ID: 55386). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 22505045, 12955719). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000083215 SCV000115289 uncertain significance Breast-ovarian cancer, familial 1 2007-03-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083215 SCV000145302 uncertain significance Breast-ovarian cancer, familial 1 2000-06-12 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.