Submissions for variant NM_001377.3(DYNC2H1):c.5876T>A (p.Ile1959Asn)

gnomAD frequency: 0.00001  dbSNP: rs756556129

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV004591457	SCV005079140	likely pathogenic	not provided	2023-12-06	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29068549)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004701584	SCV005204522	uncertain significance	not specified	2024-06-11	criteria provided, single submitter	clinical testing	Variant summary: DYNC2H1 c.5876T>A (p.Ile1959Asn) results in a non-conservative amino acid change located in the Dynein heavy chain, hydrolytic ATP-binding dynein motor region (IPR035699) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.5e-06 in 236436 control chromosomes. c.5876T>A has been reported in the literature in compound heterozygous individuals affected with Short-rib thoracic dysplasia (Zhang_2018). These data indicate that the variant may be associated with disease. 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: 446582). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV001291408	SCV005678312	likely pathogenic	Asphyxiating thoracic dystrophy 3	2024-06-11	criteria provided, single submitter	clinical testing
Dan Cohn Lab, University Of California Los Angeles	RCV001291408	SCV000611975	pathogenic	Asphyxiating thoracic dystrophy 3	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291408	SCV001479901	likely pathogenic	Asphyxiating thoracic dystrophy 3		no assertion criteria provided	research