Submissions for variant NM_001377.3(DYNC2H1):c.10900C>T (p.Pro3634Ser)

dbSNP: rs769053227

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330737	SCV004038913	uncertain significance	not specified	2023-08-10	criteria provided, single submitter	clinical testing	Variant summary: DYNC2H1 c.10921C>T (p.Pro3641Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248336 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.10921C>T has been reported in the literature as a compound heterozygous genotype together with a pathogenic variant in a neonate affected with Short-rib thoracic dysplasia (asphyxiating thoracic dystrophy) (Zhang_2018). These data do not allow any strong conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 29068549). No clinical diagnostic laboratories have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003905289	SCV004723429	pathogenic	DYNC2H1-related disorder	2024-01-22	criteria provided, single submitter	clinical testing	The DYNC2H1 c.10921C>T variant is predicted to result in the amino acid substitution p.Pro3641Ser. This variant along with another DYNC2H1 truncating variant was reported in one patient with asphyxiating thoracic dystrophy (see Table S2, Zhang et al. 2018. PubMed ID: 29068549). This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.
Dan Cohn Lab, University Of California Los Angeles	RCV000515878	SCV000611934	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515878	SCV001479887	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research