rs1223907858
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001080463.2(DYNC2H1):c.1355_1358del(p.Ile452LysfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,557,878 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. S451S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001080463.2 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 |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.1355_1358del | p.Ile452LysfsTer5 | frameshift_variant | 9/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.1355_1358del | p.Ile452LysfsTer5 | frameshift_variant | 9/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000375735.7 | c.1355_1358del | p.Ile452LysfsTer5 | frameshift_variant | 9/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000650373.2 | c.1355_1358del | p.Ile452LysfsTer5 | frameshift_variant | 9/90 | NM_001080463.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151906Hom.: 0 Cov.: 32
GnomAD4 exome AF: 7.11e-7 AC: 1AN: 1405972Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 697694
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151906Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74188
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 22, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 459277). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ile452Lysfs*5) in the DYNC2H1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at