ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.2050C>T (p.Gln684Ter) (rs387906848)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000023237 SCV000553931 pathogenic Tumor susceptibility linked to germline BAP1 mutations 2019-12-27 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the penultimate exon of the BAP1 mRNA at codon 684 (p.Gln684*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 45 amino acids of the BAP1 protein. This variant is present in population databases (rs387906848, ExAC 0.001%). This variant has been reported to segregate with mesothelioma, skin cancer and uveal melanoma in two families (PMID: 21874000, 24243779). ClinVar contains an entry for this variant (Variation ID: 30302). This variant deletes the C-terminal nuclear localization sequence of BAP1, which is required for its tumor suppressor function (PMID: 18757409). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000487149 SCV000568804 pathogenic not provided 2017-02-23 criteria provided, single submitter clinical testing This variant is denoted BAP1 c.2050C>T at the cDNA level and p.Gln684Ter (Q684X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through protein truncation. This variant has been observed to co-segregate with disease in two families with multiple cases of mesothelioma and uveal melanoma, and one mesothelioma tumor showed lack of BAP1 expression by immunohistochemistry (Testa 2011, Pilarski 2014). This variant is considered pathogenic.
Ambry Genetics RCV001014205 SCV001174887 pathogenic Hereditary cancer-predisposing syndrome 2019-03-20 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Good segregation with disease (lod 1.5-3 = 5-9 meioses);Other strong data supporting pathogenic classification;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Color RCV001014205 SCV001346840 pathogenic Hereditary cancer-predisposing syndrome 2019-09-09 criteria provided, single submitter clinical testing
OMIM RCV000023237 SCV000044528 pathogenic Tumor susceptibility linked to germline BAP1 mutations 2011-08-28 no assertion criteria provided literature only

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