rs549839617
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001206927.2(DNAH8):āc.5834A>Cā(p.Lys1945Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.5834A>C | p.Lys1945Thr | missense_variant | 42/93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.5834A>C | p.Lys1945Thr | missense_variant | 42/93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000359357.7 | c.5183A>C | p.Lys1728Thr | missense_variant | 40/91 | 2 | ENSP00000352312.3 | |||
DNAH8 | ENST00000449981.6 | c.5834A>C | p.Lys1945Thr | missense_variant | 41/82 | 5 | ENSP00000415331.2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250976Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135622
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461568Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727102
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2021 | This sequence change replaces lysine with threonine at codon 1945 of the DNAH8 protein (p.Lys1945Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is present in population databases (rs549839617, ExAC no frequency). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. 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