rs150925022
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001206927.2(DNAH8):āc.3571C>Gā(p.Pro1191Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,603,612 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā ).
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.3571C>G | p.Pro1191Ala | missense_variant | 27/93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.3571C>G | p.Pro1191Ala | missense_variant | 27/93 | 5 | NM_001206927.2 | ENSP00000333363 | P2 | |
DNAH8 | ENST00000359357.7 | c.2920C>G | p.Pro974Ala | missense_variant | 25/91 | 2 | ENSP00000352312 | A2 | ||
DNAH8 | ENST00000449981.6 | c.3571C>G | p.Pro1191Ala | missense_variant | 26/82 | 5 | ENSP00000415331 |
Frequencies
GnomAD3 genomes AF: 0.0000790 AC: 12AN: 151966Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000137 AC: 33AN: 240314Hom.: 0 AF XY: 0.000154 AC XY: 20AN XY: 129804
GnomAD4 exome AF: 0.000110 AC: 159AN: 1451646Hom.: 1 Cov.: 30 AF XY: 0.000114 AC XY: 82AN XY: 721742
GnomAD4 genome AF: 0.0000790 AC: 12AN: 151966Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74198
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 12, 2022 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1191 of the DNAH8 protein (p.Pro1191Ala). This variant is present in population databases (rs150925022, 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: 454570). 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: "Tolerated"; 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