Submissions for variant NM_001377.3(DYNC2H1):c.2818+1G>C

dbSNP: rs1591316134

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001929460	SCV002203249	pathogenic	Jeune thoracic dystrophy	2021-09-23	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 19 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). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of short-rib thoracic dysplasia with or without polydactyly (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005042538	SCV005678281	likely pathogenic	Asphyxiating thoracic dystrophy 3	2024-06-22	criteria provided, single submitter	clinical testing