ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.10142C>T (p.Pro3381Leu)

gnomAD frequency: 0.00003  dbSNP: rs368631447
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508370 SCV000603403 likely pathogenic not specified 2016-09-25 criteria provided, single submitter clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269722 SCV001449929 likely pathogenic not provided 2018-06-07 criteria provided, single submitter clinical testing
Invitae RCV000984619 SCV002145651 pathogenic Jeune thoracic dystrophy 2023-11-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3388 of the DYNC2H1 protein (p.Pro3388Leu). This variant is present in population databases (rs368631447, gnomAD 0.005%). This missense change has been observed in individual(s) with short-rib polydactyly syndrome or Jeune syndrome (PMID: 23456818, 29068549, 31415973). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 439631). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYNC2H1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Dan Cohn Lab, University Of California Los Angeles RCV001291158 SCV000611964 pathogenic Asphyxiating thoracic dystrophy 3 2017-06-01 no assertion criteria provided research
Rare Disease Group, Clinical Genetics, Karolinska Institutet RCV000984619 SCV000924634 likely pathogenic Jeune thoracic dystrophy 2018-06-19 no assertion criteria provided clinical testing The c.10163C>T variant was seen in compound heterozygous state with a frameshift variant in DYNC2H1 (c.2386del). Termination of pregnancy occurs because of lethal skeletal dysplasia. Clinical diagnosis was short-rib polydactyly syndrome, type Majewski. In summary, the Pro3388Leu meets our criteria to be classified as likely pathogenic.
University of Washington Center for Mendelian Genomics, University of Washington RCV001291158 SCV001479540 likely pathogenic Asphyxiating thoracic dystrophy 3 no assertion criteria provided research

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