chr6-38909743-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BS1_Supporting
The NM_001206927.2(DNAH8):āc.9739A>Gā(p.Arg3247Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0002 in 1,613,020 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001206927.2 missense, splice_region
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.9739A>G | p.Arg3247Gly | missense_variant, splice_region_variant | 65/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.783-1906T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.9739A>G | p.Arg3247Gly | missense_variant, splice_region_variant | 65/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.9088A>G | p.Arg3030Gly | missense_variant, splice_region_variant | 63/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.9739A>G | p.Arg3247Gly | missense_variant, splice_region_variant | 64/82 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000407 AC: 62AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000331 AC: 83AN: 250582Hom.: 0 AF XY: 0.000317 AC XY: 43AN XY: 135498
GnomAD4 exome AF: 0.000179 AC: 261AN: 1460672Hom.: 1 Cov.: 30 AF XY: 0.000191 AC XY: 139AN XY: 726726
GnomAD4 genome AF: 0.000407 AC: 62AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40AN XY: 74504
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 3247 of the DNAH8 protein (p.Arg3247Gly). This variant is present in population databases (rs146938126, gnomAD 0.1%). 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: 238659). 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 C65"). 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