rs747857715
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001080463.2(DYNC2H1):c.8050G>T(p.Gly2684Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000869 in 1,610,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G2684G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001080463.2 stop_gained
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.8050G>T | p.Gly2684Ter | stop_gained | 49/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.8050G>T | p.Gly2684Ter | stop_gained | 49/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.8050G>T | p.Gly2684Ter | stop_gained | 49/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.8050G>T | p.Gly2684Ter | stop_gained | 49/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000334267.11 | c.2205+65019G>T | intron_variant | 1 | |||||
DYNC2H1 | ENST00000649323.1 | c.*5574G>T | 3_prime_UTR_variant, NMD_transcript_variant | 47/51 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245322Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 132934
GnomAD4 exome AF: 0.00000892 AC: 13AN: 1458088Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 4AN XY: 725002
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Pathogenic:2
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Jeune thoracic dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change creates a premature translational stop signal (p.Gly2684*) 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, 33755199). This variant is present in population databases (rs747857715, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of DYNC2H1-related conditions (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 446607). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at