Submissions for variant NM_001377.3(DYNC2H1):c.10198C>T (p.Arg3400Ter)

gnomAD frequency: 0.00016  dbSNP: rs943680446

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486867	SCV000573444	pathogenic	not provided	2018-12-07	criteria provided, single submitter	clinical testing	A novel R3407X pathogenic variant was identified in the DYNC2H1 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R3407X nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R3407X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).Other known loss of function variants in this region have been reported in the Human Gene Mutation Database in association with asphyxiating thoracic dystrophy (Stenson et al., 2014), supporting the functional importance of this region of the protein.
CeGaT Center for Human Genetics Tuebingen	RCV000486867	SCV001248585	pathogenic	not provided	2019-12-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001253670	SCV002021821	pathogenic	Asphyxiating thoracic dystrophy 3	2020-10-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002526956	SCV003455317	pathogenic	Jeune thoracic dystrophy	2024-07-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg3407*) in the DYNC2H1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734, 33755199). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with short-rib polydactyly syndrome (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 423715). For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001253670	SCV005416795	pathogenic	Asphyxiating thoracic dystrophy 3		criteria provided, single submitter	clinical testing	PVS1+PM2_Supporting+PM3_Supporting+PP1
Fulgent Genetics, Fulgent Genetics	RCV001253670	SCV005678364	pathogenic	Asphyxiating thoracic dystrophy 3	2024-06-19	criteria provided, single submitter	clinical testing
Dan Cohn Lab, University Of California Los Angeles	RCV001253670	SCV000611955	pathogenic	Asphyxiating thoracic dystrophy 3	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001253670	SCV001479383	likely pathogenic	Asphyxiating thoracic dystrophy 3		no assertion criteria provided	research