ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.484C>T (p.Arg162Ter) (rs747604569)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166003 SCV000216762 pathogenic Hereditary cancer-predisposing syndrome 2017-06-16 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)
Color RCV000166003 SCV000689393 pathogenic Hereditary cancer-predisposing syndrome 2017-07-17 criteria provided, single submitter clinical testing
GeneDx RCV000484711 SCV000564810 pathogenic not provided 2017-10-26 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRIP1 c.484C>T at the cDNA level and p.Arg162Ter (R162X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant was observed in cohort of 1250 individuals with personal history of Lynch syndrome-associated cancer and/or polyps undergoing multi-gene panel testing (Yurgelun 2015). This variant is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000588178 SCV000699729 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.484C>T (p.Arg162X) variant results in a premature termination codon, predicted to cause a truncated or absent BRIP1 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.1871C>A/p.S624X). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/121388 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625). This variant has been reported in one suspected LS patient and B cell lymphoma sample. In addition, multiple clinical diagnostic laboratories classified this variant as pathogenic, without evidence to independently evaluate. Taken together, this variant is classified as likely pathogenic until more information becomes available.
Invitae RCV000198978 SCV000253961 pathogenic Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 162 (p.Arg162*). It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic. This particular variant has been reported in the literature in an individual undergoing genetic testing for Lynch syndrome (PMID: 25980754). For these reasons, this variant has been classified as Pathogenic.

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