ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4655_4658del (p.Tyr1552fs) (rs80357561)

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Total submissions: 7
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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 2018-02-22 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA1 is denoted c.4655_4658delACTT at the cDNA level and p.Tyr1552CysfsX6 (Y1552CfsX6) at the protein level. This variant would be defined as BRCA1 4774_4777delACTT using alternate nomenclature. The normal sequence, with the bases that are deleted in brackets, is TCTT[delACTT]GCCA. The deletion causes a frameshift which changes a Tyrosine to a Cysteine at codon 1552, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.4655_4658delACTT was identified in an individual referred for hereditary cancer testing (LaDuca 2017). We consider this variant to be pathogenic.
Ambry Genetics RCV000131826 SCV000186881 pathogenic Hereditary cancer-predisposing syndrome 2019-10-30 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Counsyl RCV000077581 SCV000488608 likely pathogenic Breast-ovarian cancer, familial 1 2016-05-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
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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