Submissions for variant NM_001377.3(DYNC2H1):c.3059T>G (p.Leu1020Ter)

gnomAD frequency: 0.00001  dbSNP: rs373335226

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521701	SCV000618101	likely pathogenic	not provided	2023-09-25	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Identified with a second DYNC2H1 variant in patients with skeletal dysplasia referred for genetic testing at GeneDx and in published literature (Zhang et al., 2018); This variant is associated with the following publications: (PMID: 29068549)
Invitae	RCV003748238	SCV004519589	pathogenic	Jeune thoracic dystrophy	2023-09-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu1020*) 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 (rs373335226, gnomAD 0.09%). 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: 446537). For these reasons, this variant has been classified as Pathogenic.
Dan Cohn Lab, University Of California Los Angeles	RCV001291393	SCV000611912	pathogenic	Asphyxiating thoracic dystrophy 3	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291393	SCV001479869	likely pathogenic	Asphyxiating thoracic dystrophy 3		no assertion criteria provided	research