Submissions for variant NM_001377.3(DYNC2H1):c.1953G>A (p.Lys651=)

dbSNP: rs1178331074

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000500337	SCV000598131	pathogenic	Asphyxiating thoracic dystrophy 3	2015-02-24	criteria provided, single submitter	clinical testing	This heterozygous variant in the DYNC2H1 gene (autosomal recessive transmission), inherited from the mother, was present in a foetus who also harbours a second variant in the same gene inherited by the father (compound heterozygosity).
GeneDx	RCV001764498	SCV002008664	uncertain significance	not provided	2020-10-06	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 29068549, 23456818, 27353043)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000515832	SCV004301920	pathogenic	Jeune thoracic dystrophy	2023-09-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 437419). This variant has been observed in individual(s) with short-rib polydactyly syndrome or asphyxiating thoracic dystrophy (PMID: 23456818, 27353043, 29068549). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects codon 651 of the DYNC2H1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DYNC2H1 protein. This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon.
Dan Cohn Lab, University Of California Los Angeles	RCV000515832	SCV000611942	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515832	SCV001479371	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research