rs756190655
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001206927.2(DNAH8):c.5515G>A(p.Ala1839Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.5515G>A | p.Ala1839Thr | missense_variant | 40/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.5515G>A | p.Ala1839Thr | missense_variant | 40/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.4864G>A | p.Ala1622Thr | missense_variant | 38/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.5515G>A | p.Ala1839Thr | missense_variant | 39/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251036Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135662
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461552Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727092
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74312
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2021 | This sequence change replaces alanine with threonine at codon 1839 of the DNAH8 protein (p.Ala1839Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs756190655, ExAC 0.006%). This missense change has been observed in individual(s) with clinical features of DNAH8-related conditions (Invitae). 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