rs200452908
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001369.3(DNAH5):c.1585C>T(p.Arg529Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000566 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R529Q) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.1585C>T | p.Arg529Trp | missense_variant | 12/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.1585C>T | p.Arg529Trp | missense_variant | 12/79 | 1 | NM_001369.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000243 AC: 61AN: 251166Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135748
GnomAD4 exome AF: 0.000607 AC: 887AN: 1461728Hom.: 0 Cov.: 31 AF XY: 0.000565 AC XY: 411AN XY: 727166
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 14, 2020 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 24, 2015 | - - |
Primary ciliary dyskinesia Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2016 | The p.R529W variant (also known as c.1585C>T), located in coding exon 12 of the DNAH5 gene, results from a C to T substitution at nucleotide position 1585. The arginine at codon 529 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs200452908. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0% (0/2098) total alleles studied.. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.03% (4/13004) total alleles studied and 0.05% (4/8600) European American alleles. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at