rs148767488
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001206927.2(DNAH8):c.5185A>C(p.Lys1729Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.5185A>C | p.Lys1729Gln | 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.5185A>C | p.Lys1729Gln | missense_variant | Exon 37 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000359357.7 | c.4534A>C | p.Lys1512Gln | missense_variant | Exon 35 of 91 | 2 | ENSP00000352312.3 | |||
DNAH8 | ENST00000449981.6 | c.5185A>C | p.Lys1729Gln | missense_variant | Exon 36 of 82 | 5 | ENSP00000415331.2 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000199 AC: 50AN: 250944Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135626
GnomAD4 exome AF: 0.000296 AC: 433AN: 1461142Hom.: 0 Cov.: 30 AF XY: 0.000277 AC XY: 201AN XY: 726880
GnomAD4 genome AF: 0.000217 AC: 33AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74454
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
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This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1729 of the DNAH8 protein (p.Lys1729Gln). This variant is present in population databases (rs148767488, gnomAD 0.03%). 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: 407298). 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 C45"). 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. -
not specified Uncertain:1
The c.5185A>C (p.K1729Q) alteration is located in exon 37 (coding exon 36) of the DNAH8 gene. This alteration results from a A to C substitution at nucleotide position 5185, causing the lysine (K) at amino acid position 1729 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at