ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5387C>A (p.Ser1796Ter) (rs80357055)

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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 RCV000162886 SCV000213373 pathogenic Hereditary cancer-predisposing syndrome 2017-10-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031244 SCV000145486 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031244 SCV000300253 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 RCV000522547 SCV000617444 pathogenic not provided 2018-04-10 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5387C>A at the cDNA level and p.Ser1796Ter (S1796X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as BRCA1 5506C>A using alternate nomenclature, has been reported in at least three African American women with breast cancer (Haffty 2009, Pal 2013, Pal 2015) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048970 SCV000699250 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-20 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5387C>A (p.Ser1796X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.5444G>A [p.Trp1815X], c.5503C>T [p.Arg1835X], and c.5510G>A [p.Trp1837X]). One in silico tool predicts a damaging outcome for this variant. This variant is absent in ExAC (0/121152 control chromosomes), which is a large control population exome database. Multiple publications cite the variant in affected individuals, predominantly African Americans. In addition, multiple clinical diagnostic laboratories/databases classify the variant as "pathogenic." Taken together, this variant is classified as pathogenic.
Invitae RCV000048970 SCV000076983 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1796 (p.Ser1796*) of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in the literature in individuals affected with breast cancer (PMID: 23320992, 19491284). This variant is also known as c.5506C>A in the literature. ClinVar contains an entry for this variant (Variation ID: 37663). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031244 SCV000296358 pathogenic Breast-ovarian cancer, familial 1 2015-07-06 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031244 SCV000053848 pathogenic Breast-ovarian cancer, familial 1 2010-04-30 no assertion criteria provided clinical testing

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