Submissions for variant NM_001369.3(DNAH5):c.11583C>A (p.Ser3861Arg)

gnomAD frequency: 0.00003  dbSNP: rs576096758

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000439859	SCV000520925	uncertain significance	not provided	2024-06-24	criteria provided, single submitter	clinical testing	Identified in two patients in published literature with primary ciliary dyskinesia who harbored another DNAH5 variant on the opposite allele (in trans), but one of these patients was also reported to harbor another DNAH5 variant on the same allele (in cis) with p.(S3861R) as well (PMID: 26228299, 27637300); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22416021, 34426522, 26228299, 27637300)
Illumina Laboratory Services, Illumina	RCV001155590	SCV001317028	uncertain significance	Primary ciliary dyskinesia 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001155590	SCV001369859	uncertain significance	Primary ciliary dyskinesia 3	2020-03-12	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP3.
Genome-Nilou Lab	RCV001155590	SCV001716349	uncertain significance	Primary ciliary dyskinesia 3	2021-05-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001835797	SCV002622433	uncertain significance	Primary ciliary dyskinesia	2018-03-16	criteria provided, single submitter	clinical testing	The p.S3861R variant (also known as c.11583C>A), located in coding exon 68 of the DNAH5 gene, results from a C to A substitution at nucleotide position 11583. The serine at codon 3861 is replaced by arginine, an amino acid with dissimilar properties. This variant was reported in a Czech individual with primary ciliary dyskinesia (PCD); however, only selected DNAH5 exons were analyzed and a second DNAH5 variant was not reported (Djakow J et al. Pediatr. Pulmonol., 2012 Sep;47:864-75). In addition, this variant was confirmed in trans with a frameshift alteration in a an adult with situs inversus, rhinitis, sinusitis, bronchitis, bronchopneumonia, asthma, and outer dynein arm defect on electron microscopy (Boaretto F et al. J Mol Diagn, 2016 11;18:912-922). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV001155590	SCV002777865	uncertain significance	Primary ciliary dyskinesia 3	2022-04-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001835797	SCV003272320	benign	Primary ciliary dyskinesia	2025-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001835797	SCV002078426	uncertain significance	Primary ciliary dyskinesia	2020-02-12	no assertion criteria provided	clinical testing