Submissions for variant NM_001372.4(DNAH9):c.308dup (p.Leu104fs)

dbSNP: rs769795916

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001584455	SCV001818963	pathogenic	not provided	2022-06-29	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30471718, 34426522, 33963417, 33610189)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001584455	SCV002142785	pathogenic	not provided	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu104Profs*45) in the DNAH9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH9 are known to be pathogenic (PMID: 30471718). This variant is present in population databases (rs773305837, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 30471718). 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: 523437). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001584455	SCV004142023	pathogenic	not provided	2023-08-01	criteria provided, single submitter	clinical testing	DNAH9: PVS1, PM2
Revvity Omics, Revvity	RCV001270165	SCV004234737	pathogenic	Ciliary dyskinesia, primary, 40	2023-03-30	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001270165	SCV005415974	pathogenic	Ciliary dyskinesia, primary, 40		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PM3_Strong
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626803	SCV000747506	uncertain significance	Abnormal cardiovascular system morphology	2017-01-01	flagged submission	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001270165	SCV001368978	uncertain significance	Ciliary dyskinesia, primary, 40	2016-01-01	flagged submission	clinical testing	This variant was classified as: Uncertain significance. This variant was inherited from a parent.
Institute of Human Genetics, University of Wuerzburg	RCV001619814	SCV001847697	likely pathogenic	Hydrocephalus		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004748865	SCV005362694	pathogenic	DNAH9-related disorder	2024-08-25	no assertion criteria provided	clinical testing	The DNAH9 c.308dupT variant is predicted to result in a frameshift and premature protein termination (p.Leu104Profs*45). This variant, along with other variants in DNAH9, has been reported in individuals with laterality defects and cardiac anomalies (Loges et al. 2018. PubMed ID: 30471718; Miletic et al. 2021. PubMed ID: 33963417; reported as c.302dupT, F6-II, Chen et al. 2022. PubMed ID: 35050399; De Jesús-Rojas et al. 2022. PubMed ID: 35626283). Of note, in one case the variant were confirmed to be in the compound heterozygous state (Miletic et al. 2021. PubMed ID: 33963417). This variant is reported in 0.052% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in DNAH9 are expected to be pathogenic. This variant is interpreted as pathogenic.