Submissions for variant NM_001377.3(DYNC2H1):c.1306G>T (p.Glu436Ter)

gnomAD frequency: 0.00003  dbSNP: rs371011047

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000516025	SCV000788376	pathogenic	Jeune thoracic dystrophy	2018-05-01	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000516025	SCV003482110	pathogenic	Jeune thoracic dystrophy	2022-06-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 446556). This premature translational stop signal has been observed in individual(s) with short-rib thoracic dysplasia (SRTD) with or without polydactyly (PMID: 23456818, 29068549). 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. This sequence change creates a premature translational stop signal (p.Glu436*) in the DYNC2H1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734).
Dan Cohn Lab, University Of California Los Angeles	RCV000516025	SCV000611935	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000516025	SCV001479888	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001353119	SCV001548280	pathogenic	Asphyxiating thoracic dystrophy 3		no assertion criteria provided	research