ClinVar Miner

Submissions for variant NM_002437.5(MPV17):c.186+2T>C

gnomAD frequency: 0.00012  dbSNP: rs147952488
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195573 SCV000251737 pathogenic not provided 2020-03-09 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29318572, 23137571, 29282788, 22593919, 20074988)
Labcorp Genetics (formerly Invitae), Labcorp RCV000195573 SCV001377454 likely pathogenic not provided 2024-02-02 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the MPV17 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). This variant is present in population databases (rs147952488, gnomAD 0.03%). Disruption of this splice site has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 20074988). ClinVar contains an entry for this variant (Variation ID: 38347). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000031903 SCV001445920 pathogenic Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) 2019-05-24 criteria provided, single submitter clinical testing This variant affects the canonical splice donor site of intron 3 of 7, and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has been previously reported as a compound heterozygous change in patients with hepatocerebral mitochondrial DNA depletion syndrome (PMID: 20074988), and has been classified as Pathogenic by another clinical diagnostic laboratory in the ClinVar database (Variation ID: 38347). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.003% (8/277190) and thus is presumed to be rare. Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing. Based on the available evidence, the c.186+2T>C variant is classified as Pathogenic.
Revvity Omics, Revvity RCV000195573 SCV003819630 pathogenic not provided 2022-06-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466880 SCV004193738 pathogenic Charcot-Marie-Tooth disease, axonal, type 2EE 2024-03-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005025084 SCV005655956 pathogenic Mitochondrial DNA depletion syndrome 6 (hepatocerebral type); Charcot-Marie-Tooth disease, axonal, type 2EE 2024-05-04 criteria provided, single submitter clinical testing

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