ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.11493+2T>A (rs1555096711)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579324 SCV000681245 likely pathogenic not provided 2017-12-11 criteria provided, single submitter clinical testing The c.11514+2 T>A splice site variant in the DYNC2H1 gene destroys the canonical splice donor site in intron 79. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.11514+2 T>A variant is not observed in large population cohorts (Lek et al., 2016). Although this pathogenic variant has not been previously reported to our knowledge, we consider it to be a likely pathogenic variant; however, the possibility that it is benign cannot be excluded.
Invitae RCV000823429 SCV000964289 likely pathogenic Jeune thoracic dystrophy 2018-10-01 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 79 of the DYNC2H1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Jeune syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 489251). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108). 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.

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