ClinVar Miner

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

dbSNP: rs80358345
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166817 SCV000217631 likely pathogenic Hereditary cancer-predisposing syndrome 2023-01-30 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. This results in the in-frame deletion of an alanine at codon 1693. This alteration (also designated as c.5196del3 and c.5197_5199del3 in the literature) has been identified in Spanish breast and ovarian cancer cohorts (Diez, O et al. Hum Mutat. 2003 Oct;22(4):301-12; Pajares B et al. BMC Cancer 2018 Jun;18(1):647). This alteration was deleterious in a transcriptional activation assay (Nepomuceno TC et al. Sci Rep 2022 Sep;12(1):16203). RNA studies have shown this variant to result in the in-frame deletion of coding exon 16 (Campos, B et al. Hum Mutat. 2003 Oct;22(4):337; Houdayer, C et al. Hum Mutat. 2012 Aug;33(8):1228-38). 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, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Genologica Medica RCV000083215 SCV000577933 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001379223 SCV001576984 likely pathogenic Hereditary breast ovarian cancer syndrome 2022-12-18 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 55386). This variant is also known as 5197_5199del3. This variant has been observed in individual(s) with breast and/or ovarian cancer (PMID: 12955716, 29446198, 29884136). This variant is not present in population databases (gnomAD no frequency). 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.
Baylor Genetics RCV000083215 SCV004215089 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2023-06-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083215 SCV000115289 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2007-03-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083215 SCV000145302 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2000-06-12 no assertion criteria provided clinical testing

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