ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.121G>A (p.Gly41Ser) (rs372586694)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657126 SCV000279953 uncertain significance not provided 2018-08-20 criteria provided, single submitter clinical testing This variant is denoted BAP1 c.121G>A at the cDNA level, p.Gly41Ser (G41S) at the protein level, and results in the change of a Glycine to a Serine (GGC>AGC). This variant has been identified in at least one individual with a personal and family history of renal cell carcinoma, however tumor testing suggested that the variant did not segregate with disease in this family (Pe?a-Llopis 2012, Farley 2013). This variant was also identified in a patient with malignant pleural mesothelioma as well as 1/118 healthy Hispanic individuals undergoing whole genome sequencing (Bodian 2014, De Rienzo 2015). Of note, the participants in the Bodian et al. study were younger than 50 years old thus the unaffected status of this individual may not be significant. BAP1 Gly41Ser was observed at an allele frequency of 0.44% (134/30,782) in individuals of South Asian ancestry in large population cohorts. This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether BAP1 Gly41Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000308261 SCV000445488 benign Tumor susceptibility linked to germline BAP1 mutations 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000308261 SCV000563751 benign Tumor susceptibility linked to germline BAP1 mutations 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000562698 SCV000672740 likely benign Hereditary cancer-predisposing syndrome 2018-06-28 criteria provided, single submitter clinical testing In silico models in agreement (benign);Does not segregate with disease in family study (genes with incomplete penetrance)
Mendelics RCV000308261 SCV000838045 uncertain significance Tumor susceptibility linked to germline BAP1 mutations 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000562698 SCV000902645 benign Hereditary cancer-predisposing syndrome 2016-07-20 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000657126 SCV001153971 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
ITMI RCV000120195 SCV000084341 not provided not specified 2013-09-19 no assertion provided reference population

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