Submissions for variant NM_001377.3(DYNC2H1):c.1949T>A (p.Ile650Asn)

dbSNP: rs1555041449

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004701582	SCV005202645	uncertain significance	not specified	2024-07-11	criteria provided, single submitter	clinical testing	Variant summary: DYNC2H1 c.1949T>A (p.Ile650Asn) results in a non-conservative amino acid change located in the Dynein heavy chain, tail (IPR013594) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 242452 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1949T>A has been reported in the literature in at least one compound heterozygous individual affected with Short-rib thoracic dysplasia (e.g. Zhang_2019). These data do not provide sufficient evidence to 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: 446541). Based on the evidence outlined above, the variant was classified as uncertain significance.
Dan Cohn Lab, University Of California Los Angeles	RCV001291396	SCV000611916	pathogenic	Asphyxiating thoracic dystrophy 3	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291396	SCV001479872	likely pathogenic	Asphyxiating thoracic dystrophy 3		no assertion criteria provided	research