ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.5959A>G (p.Thr1987Ala)

dbSNP: rs137853035
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520054 SCV000617825 likely pathogenic not provided 2017-10-16 criteria provided, single submitter clinical testing The T1987A variant in the DYNC2H1 gene has been reported previously in three fetuses diagnosed with short rib polydactyly type III in a single family (Dagoneau et al., 2009). The T1987A variant is not observed in large population cohorts (Lek et al., 2016). The T1987A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T1987A as a likely pathogenic variant.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000006886 SCV001474570 likely pathogenic Asphyxiating thoracic dystrophy 3 2019-10-24 criteria provided, single submitter clinical testing The DYNC2H1 p.Thr1987Ala variant (rs137853035; ClinVar Variation ID 6513), has been previously observed in three siblings with an antenatal diagnosis of short rib polydactyly syndrome (SRP) type III (Dagoneau 2009). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The threonine at codon 1987 is highly conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on the available information, this variant is considered likely pathogenic. References: Dagoneau N et al. DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III. Am J Hum Genet. 2009 May;84(5):706-11.
OMIM RCV000006886 SCV000027082 pathogenic Asphyxiating thoracic dystrophy 3 2009-05-01 no assertion criteria provided literature only

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.