rs45461493
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001206927.2(DNAH8):c.5171G>A(p.Gly1724Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,613,320 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001206927.2 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.5171G>A | p.Gly1724Asp | missense_variant | Exon 37 of 93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.5171G>A | p.Gly1724Asp | missense_variant | Exon 37 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000359357.7 | c.4520G>A | p.Gly1507Asp | missense_variant | Exon 35 of 91 | 2 | ENSP00000352312.3 | |||
DNAH8 | ENST00000449981.6 | c.5171G>A | p.Gly1724Asp | missense_variant | Exon 36 of 82 | 5 | ENSP00000415331.2 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000203 AC: 51AN: 251048Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135710
GnomAD4 exome AF: 0.000384 AC: 561AN: 1461260Hom.: 1 Cov.: 30 AF XY: 0.000371 AC XY: 270AN XY: 726924
GnomAD4 genome AF: 0.000132 AC: 20AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74268
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.5171G>A (p.G1724D) alteration is located in exon 37 (coding exon 36) of the DNAH8 gene. This alteration results from a G to A substitution at nucleotide position 5171, causing the glycine (G) at amino acid position 1724 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Primary ciliary dyskinesia Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1724 of the DNAH8 protein (p.Gly1724Asp). This variant is present in population databases (rs45461493, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 454576). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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