Submissions for variant NM_001377.3(DYNC2H1):c.5558+2T>C

dbSNP: rs762666243

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000515862	SCV004540595	likely pathogenic	Jeune thoracic dystrophy	2023-09-23	criteria provided, single submitter	clinical testing	Disruption of this splice site has been observed in individual(s) with short-rib thoracic dysplasia (SRTD) with or without polydactyly (PMID: 29068549, 33694158). This sequence change affects a donor splice site in intron 35 of the DYNC2H1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734, 33755199). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. ClinVar contains an entry for this variant (Variation ID: 446578). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Dan Cohn Lab, University Of California Los Angeles	RCV000515862	SCV000611971	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515862	SCV001479561	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research