Submissions for variant NM_001369.3(DNAH5):c.7914dup (p.Arg2639fs)

dbSNP: rs749082955

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000533129	SCV000624294	pathogenic	Primary ciliary dyskinesia	2024-08-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg2639Thrfs*19) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). This variant is present in population databases (rs749082955, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 16627867). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 454806). For these reasons, this variant has been classified as Pathogenic.
Natera, Inc.	RCV000533129	SCV002080857	pathogenic	Primary ciliary dyskinesia	2020-09-13	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935395	SCV004748128	pathogenic	DNAH5-related disorder	2023-12-11	no assertion criteria provided	clinical testing	The DNAH5 c.7914dupA variant is predicted to result in a frameshift and premature protein termination (p.Arg2639Thrfs*19). This variant has been reported in the compound heterozygous state with a second pathogenic DNAH5 variant in an individual with primary ciliary dyskinesia (Hornef et al. 2006. PubMed ID: 16627867). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in DNAH5 are expected to be pathogenic. This variant is interpreted as pathogenic.