ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.1217A>C (p.Glu406Ala)

dbSNP: rs535695655
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000459467 SCV000553950 uncertain significance BAP1-related tumor predisposition syndrome 2025-02-03 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 406 of the BAP1 protein (p.Glu406Ala). This variant is present in population databases (rs535695655, gnomAD 0.005%). This missense change has been observed in individual(s) with melanoma (PMID: 28062663, 36863448). ClinVar contains an entry for this variant (Variation ID: 412424). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BAP1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000574088 SCV000672785 likely benign Hereditary cancer-predisposing syndrome 2021-05-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000574088 SCV000687910 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-06 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with alanine at codon 406 of the BAP1 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with melanoma (PMID: 28062663). This variant has also been identified in 7/248872 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001534230 SCV001751135 uncertain significance not provided 2024-05-16 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in individual(s) with melanoma (PMID: 28062663); This variant is associated with the following publications: (PMID: 28062663)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001534230 SCV002009781 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Baylor Genetics RCV000459467 SCV004214905 uncertain significance BAP1-related tumor predisposition syndrome 2023-05-11 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000459467 SCV005404725 likely benign BAP1-related tumor predisposition syndrome 2024-07-15 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

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