Submissions for variant NM_001277115.2(DNAH11):c.10472G>A (p.Arg3491His)

gnomAD frequency: 0.00048  dbSNP: rs370932895

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723974	SCV000231916	uncertain significance	not provided	2014-07-18	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218296	SCV000271685	uncertain significance	not specified	2017-02-23	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
Invitae	RCV000226017	SCV000286970	benign	Primary ciliary dyskinesia	2024-01-30	criteria provided, single submitter	clinical testing
Center for Personalized Medicine, Children's Hospital Los Angeles	RCV000735289	SCV000854442	uncertain significance	Cleft upper lip; Cognitive impairment; Median cleft upper lip; Bifid ribs; Asymmetry of the thorax; Periventricular leukomalacia; Cleft palate		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000723974	SCV001155048	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001160743	SCV001322566	uncertain significance	Primary ciliary dyskinesia 7	2018-01-12	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.
Ambry Genetics	RCV000226017	SCV002704127	uncertain significance	Primary ciliary dyskinesia	2018-07-05	criteria provided, single submitter	clinical testing	The p.R3491H variant (also known as c.10472G>A), located in coding exon 64 of the DNAH11 gene, results from a G to A substitution at nucleotide position 10472. The arginine at codon 3491 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV001160743	SCV002801340	uncertain significance	Primary ciliary dyskinesia 7	2022-02-24	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001160743	SCV003843232	uncertain significance	Primary ciliary dyskinesia 7	2021-01-29	criteria provided, single submitter	clinical testing	This variant was observed in compound heterozygosity with variant c.1848+1G>T
PreventionGenetics, part of Exact Sciences	RCV003917675	SCV004727937	uncertain significance	DNAH11-related condition	2024-01-09	criteria provided, single submitter	clinical testing	The DNAH11 c.10472G>A variant is predicted to result in the amino acid substitution p.Arg3491His. This variant has been reported in the homozygous state in an individual with skeletal anomalies and cognitive impairment who also carries a homozygous truncating variant in TMCO1 (Ji et al. 2019. PubMed ID: 30755392). This variant is reported in 0.17% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx	RCV000723974	SCV001791033	likely pathogenic	not provided	2023-08-29	flagged submission	clinical testing	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: 30755392, 35586607, 37035737)
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000723974	SCV001799037	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000723974	SCV001967880	uncertain significance	not provided		no assertion criteria provided	clinical testing