rs373906923
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_015512.5(DNAH1):c.6293G>A(p.Arg2098His) variant causes a missense change. The variant allele was found at a frequency of 0.000189 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015512.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.6293G>A | p.Arg2098His | missense_variant | 40/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.6362G>A | p.Arg2121His | missense_variant | 42/80 | ||
DNAH1 | XM_017006130.2 | c.6293G>A | p.Arg2098His | missense_variant | 41/79 | ||
DNAH1 | XM_017006131.2 | c.6362G>A | p.Arg2121His | missense_variant | 42/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.6293G>A | p.Arg2098His | missense_variant | 40/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.6554G>A | non_coding_transcript_exon_variant | 40/77 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000237 AC: 59AN: 249116Hom.: 0 AF XY: 0.000222 AC XY: 30AN XY: 135194
GnomAD4 exome AF: 0.000192 AC: 281AN: 1461654Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 147AN XY: 727112
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74470
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2098 of the DNAH1 protein (p.Arg2098His). This variant is present in population databases (rs373906923, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 478476). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Nov 11, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2021 | 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 - |
DNAH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 01, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at