Submissions for variant NM_001369.3(DNAH5):c.1114A>G (p.Thr372Ala)

gnomAD frequency: 0.00042  dbSNP: rs140227610

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Johns Hopkins Genomics, Johns Hopkins University	RCV001543694	SCV001762392	uncertain significance	Primary ciliary dyskinesia 3	2021-06-09	criteria provided, single submitter	clinical testing	DNAH5 c.1114A>G (rs140227610) has been identified in a large population dataset and the minor allele frequency is neither low enough to consider the variant rare (<0.1%) nor high enough to consider it a population polymorphism (>1%) within the African/African-American subpopulation (gnomAD: 34/24834 alleles; 0.14%, no homozygotes). This variant has not been reported in ClinVar nor the literature to our knowledge. Three bioinformatic tools queried predict that this substitution would be tolerated and the threonine residue at this position is evolutionarily conserved across most mammalian species assessed. We consider the clinical significance of c.1114A>G to be uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002071964	SCV002397071	likely benign	Primary ciliary dyskinesia	2025-01-23	criteria provided, single submitter	clinical testing
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	RCV002071964	SCV002573556	uncertain significance	Primary ciliary dyskinesia	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002071964	SCV002746584	likely benign	Primary ciliary dyskinesia	2022-05-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV004774458	SCV005384060	uncertain significance	not provided	2023-12-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Mayo Clinic Laboratories, Mayo Clinic	RCV004774458	SCV005411777	uncertain significance	not provided	2024-08-07	criteria provided, single submitter	clinical testing	BP4
PreventionGenetics, part of Exact Sciences	RCV004743545	SCV005344633	uncertain significance	DNAH5-related disorder	2024-07-22	no assertion criteria provided	clinical testing	The DNAH5 c.1114A>G variant is predicted to result in the amino acid substitution p.Thr372Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.14% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.