Submissions for variant NM_001369.3(DNAH5):c.8030G>A (p.Arg2677Gln)

gnomAD frequency: 0.00001  dbSNP: rs886043448

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000369132	SCV000340209	uncertain significance	not provided	2016-03-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000558292	SCV000624296	pathogenic	Primary ciliary dyskinesia	2025-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2677 of the DNAH5 protein (p.Arg2677Gln). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individual(s) with primary ciliary dyskinesia (PMID: 24150548). ClinVar contains an entry for this variant (Variation ID: 286676). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DNAH5 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000558292	SCV002681159	likely pathogenic	Primary ciliary dyskinesia	2016-12-27	criteria provided, single submitter	clinical testing	The p.R2677Q variant (also known as c.8030G>A), located in coding exon 49 of the DNAH5 gene, results from a G to A substitution at nucleotide position 8030. The arginine at codon 2677 is replaced by glutamine, an amino acid with highly similar properties. This variant was detected in a homozygous individual with chronic rhinosinusitis, recurrent respiratory infections, bronchiectasis, and left-right laterality defects; her parents were confirmed heterozygous for this variant (Zhang J et al. Eur Arch Otorhinolaryngol, 2014 Jun;271:1589-94). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV001257434	SCV005668850	likely pathogenic	Primary ciliary dyskinesia 3	2024-04-16	criteria provided, single submitter	clinical testing
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001257434	SCV001433991	likely pathogenic	Primary ciliary dyskinesia 3	2020-07-07	no assertion criteria provided	clinical testing