6-38722804-CGGGGGAT-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_001206927.2(DNAH8):c.-3_4delGGGATGG(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
DNAH8
NM_001206927.2 frameshift, start_lost
NM_001206927.2 frameshift, start_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.244
Genes affected
DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.-3_4delGGGATGG | p.Met1fs | frameshift_variant, start_lost | 2/93 | ENST00000327475.11 | NP_001193856.1 | |
DNAH8 | NM_001206927.2 | c.-3_4delGGGATGG | 5_prime_UTR_variant | 2/93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.-3_4delGGGATGG | p.Met1fs | frameshift_variant, start_lost | 2/93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000327475 | c.-3_4delGGGATGG | 5_prime_UTR_variant | 2/93 | 5 | NM_001206927.2 | ENSP00000333363.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | DNAH8: PM2, PVS1:Supporting - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.