Submissions for variant NM_001377.3(DYNC2H1):c.6866T>C (p.Leu2289Pro)

gnomAD frequency: 0.00001  dbSNP: rs1555061205

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV003233664	SCV003932214	uncertain significance	not provided	2023-03-21	criteria provided, single submitter	clinical testing	PM1, PM2,
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689771	SCV005185188	uncertain significance	not specified	2024-05-21	criteria provided, single submitter	clinical testing	Variant summary: DYNC2H1 c.6866T>C (p.Leu2289Pro) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.2e-07 in 1611598 control chromosomes. c.6866T>C has been reported in the literature in compound heterozygous state with a pathogenic variant in an individual affected with Short-rib thoracic dysplasia (Zhang_2018). These data do not allow any 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). ClinVar contains an entry for this variant (Variation ID: 446594). Based on the evidence outlined above, the variant was classified as uncertain significance.
Dan Cohn Lab, University Of California Los Angeles	RCV001291281	SCV000611994	pathogenic	Asphyxiating thoracic dystrophy 3	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291281	SCV001479728	likely pathogenic	Asphyxiating thoracic dystrophy 3		no assertion criteria provided	research