6-39026579-G-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1
The NM_001206927.2(DNAH8):c.13748G>T(p.Arg4583Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,086 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4583C) has been classified as Likely benign.
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.13748G>T | p.Arg4583Leu | missense_variant | 92/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.13748G>T | p.Arg4583Leu | missense_variant | 92/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.13097G>T | p.Arg4366Leu | missense_variant | 90/91 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152054Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000268 AC: 67AN: 249930Hom.: 0 AF XY: 0.000237 AC XY: 32AN XY: 135092
GnomAD4 exome AF: 0.0000910 AC: 133AN: 1460914Hom.: 0 Cov.: 31 AF XY: 0.0000881 AC XY: 64AN XY: 726656
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74404
ClinVar
Submissions by phenotype
DNAH8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 14, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at