chr3-52322641-GCC-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015512.5(DNAH1):c.202_203del(p.Pro68ThrfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A67A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_015512.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.202_203del | p.Pro68ThrfsTer18 | frameshift_variant | 2/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.202_203del | p.Pro68ThrfsTer18 | frameshift_variant | 3/80 | ||
DNAH1 | XM_017006130.2 | c.202_203del | p.Pro68ThrfsTer18 | frameshift_variant | 3/79 | ||
DNAH1 | XM_017006131.2 | c.202_203del | p.Pro68ThrfsTer18 | frameshift_variant | 3/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.202_203del | p.Pro68ThrfsTer18 | frameshift_variant | 2/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.463_464del | non_coding_transcript_exon_variant | 2/77 | 2 | ||||
DNAH1 | ENST00000497875.1 | n.367_368del | non_coding_transcript_exon_variant | 3/21 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461662Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727120
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro68Thrfs*18) in the DNAH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH1 are known to be pathogenic (PMID: 27573432, 27798045). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.