Submissions for variant NM_001369.3(DNAH5):c.6970A>G (p.Thr2324Ala)

gnomAD frequency: 0.00009  dbSNP: rs143074036

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000541637	SCV000624286	likely benign	Primary ciliary dyskinesia	2025-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001152114	SCV001313321	uncertain significance	Primary ciliary dyskinesia 3	2018-02-09	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	RCV000541637	SCV001431730	uncertain significance	Primary ciliary dyskinesia	2019-03-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000541637	SCV002663946	uncertain significance	Primary ciliary dyskinesia	2022-01-13	criteria provided, single submitter	clinical testing	The p.T2324A variant (also known as c.6970A>G), located in coding exon 42 of the DNAH5 gene, results from an A to G substitution at nucleotide position 6970. The threonine at codon 2324 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV001152114	SCV002776444	uncertain significance	Primary ciliary dyskinesia 3	2021-11-02	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000541637	SCV001457553	uncertain significance	Primary ciliary dyskinesia	2019-10-28	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004742485	SCV005361891	uncertain significance	DNAH5-related disorder	2024-05-09	no assertion criteria provided	clinical testing	The DNAH5 c.6970A>G variant is predicted to result in the amino acid substitution p.Thr2324Ala. This variant has been reported in the heterozygous state in an individual with primary ciliary dyskinesia (Table E2, Similuk et al. 2022. PubMed ID: 35753512). That individual was also heterozygous for the c.8440_8447del and c.2504T>A (p.Met835Lys) variants; however, the phase was not specified. This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.