chr11-103109575-AT-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001377.3(DYNC2H1):c.2delT(p.Met1ArgfsTer23) variant causes a frameshift, start lost change. The variant allele was found at a frequency of 0.00000434 in 1,612,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001377.3 frameshift, start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.2delT | p.Met1ArgfsTer23 | frameshift_variant, start_lost | Exon 1 of 90 | ENST00000650373.2 | NP_001073932.1 | |
DYNC2H1 | NM_001377.3 | c.2delT | p.Met1ArgfsTer23 | frameshift_variant, start_lost | Exon 1 of 89 | ENST00000375735.7 | NP_001368.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.2delT | p.Met1ArgfsTer23 | frameshift_variant, start_lost | Exon 1 of 90 | NM_001080463.2 | ENSP00000497174.1 | |||
DYNC2H1 | ENST00000375735.7 | c.2delT | p.Met1ArgfsTer23 | frameshift_variant, start_lost | Exon 1 of 89 | 1 | NM_001377.3 | ENSP00000364887.2 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151688Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248292Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134678
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460584Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726504
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151688Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74060
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Uncertain:1
This sequence change affects the initiator methionine of the DYNC2H1 mRNA. The next in-frame methionine is located at codon 24. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with DYNC2H1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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