5-13810137-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001369.3(DNAH5):c.7531C>G(p.Arg2511Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000581 in 1,549,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.7531C>G | p.Arg2511Gly | missense_variant | Exon 45 of 79 | 1 | NM_001369.3 | ENSP00000265104.4 | ||
DNAH5 | ENST00000681290.1 | c.7486C>G | p.Arg2496Gly | missense_variant | Exon 45 of 79 | ENSP00000505288.1 | ||||
DNAH5 | ENST00000512443.1 | n.387C>G | non_coding_transcript_exon_variant | Exon 1 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000573 AC: 8AN: 1397122Hom.: 0 Cov.: 34 AF XY: 0.00000581 AC XY: 4AN XY: 688984
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:3
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The p.R2511G variant (also known as c.7531C>G), located in coding exon 45 of the DNAH5 gene, results from a C to G substitution at nucleotide position 7531. The arginine at codon 2511 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
This sequence change replaces arginine with glycine at codon 2511 of the DNAH5 protein (p.Arg2511Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with DNAH5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at