ClinVar Miner

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

gnomAD frequency: 0.00003  dbSNP: rs368631447
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000984619 SCV002145651 pathogenic Jeune thoracic dystrophy 2024-03-13 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.
GeneDx RCV001269722 SCV005325080 likely pathogenic not provided 2023-06-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29068549, 31415973, 33726816, 35783601, 23456818)
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001291158 SCV005417560 likely pathogenic Asphyxiating thoracic dystrophy 3 criteria provided, single submitter clinical testing PM2_Supporting+PM3_Strong+PP4
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 pathogenic Jeune thoracic dystrophy 2024-09-09 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. There are at least four other individuals reported in ClinVar (Variation ID: 439631). In summary, the Pro3388Leu meets our criteria to be classified as pathogenic.
University of Washington Center for Mendelian Genomics, University of Washington RCV001291158 SCV001479540 likely pathogenic Asphyxiating thoracic dystrophy 3 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.