11-103121028-CAATT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001080463.2(DYNC2H1):βc.1355_1358delβ(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 (β ). 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