ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4655_4658del (p.Tyr1552fs) (rs80357561)

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Total submissions: 10
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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) RCV000077581 SCV000300151 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000074597 SCV000108682 pathogenic not provided 2020-11-10 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 an individual referred for hereditary cancer testing (LaDuca 2017); Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.4774_4777delACTT; This variant is associated with the following publications: (PMID: 28152038, 16267036, 32719484)
Ambry Genetics RCV000131826 SCV000186881 pathogenic Hereditary cancer-predisposing syndrome 2019-10-30 criteria provided, single submitter clinical testing The c.4655_4658delACTT pathogenic mutation, located in coding exon 13 of the BRCA1 gene, results from a deletion of 4 nucleotides at nucleotide positions 4655 to 4658, causing a translational frameshift with a predicted alternate stop codon (p.Y1552Cfs*6). This alteration has been identified in an individual who was referred for whole exome sequencing (LaDuca H et al. PLoS ONE, 2017 Feb;12:e0170843). 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.
Counsyl RCV000077581 SCV000488608 likely pathogenic Breast-ovarian cancer, familial 1 2016-05-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588044 SCV000699162 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-08 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4655_4658delACTT (p.Tyr1552Cysfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 121364 control chromosomes. A publication, Judkins_2005, cites the variant in at least 1 affected individual. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Color Health, Inc RCV000131826 SCV001354776 pathogenic Hereditary cancer-predisposing syndrome 2019-09-19 criteria provided, single submitter clinical testing
Invitae RCV000588044 SCV001590573 pathogenic Hereditary breast and ovarian cancer syndrome 2019-09-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1552Cysfs*6) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55252). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research and Development, ARUP Laboratories RCV001663921 SCV001878701 pathogenic Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2018-04-01 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000077581 SCV000109384 pathogenic Breast-ovarian cancer, familial 1 2009-06-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077581 SCV000145140 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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