rs964711006
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP3PP5_Moderate
The NM_001080463.2(DYNC2H1):c.7984C>T(p.Arg2662Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,610,814 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 Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2662Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001080463.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.7984C>T | p.Arg2662Trp | missense_variant | 49/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.7984C>T | p.Arg2662Trp | missense_variant | 49/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.7984C>T | p.Arg2662Trp | missense_variant | 49/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.7984C>T | p.Arg2662Trp | missense_variant | 49/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000334267.11 | c.2205+64953C>T | intron_variant | 1 | |||||
DYNC2H1 | ENST00000649323.1 | c.*5508C>T | 3_prime_UTR_variant, NMD_transcript_variant | 47/51 |
Frequencies
GnomAD3 genomes ? AF: 0.00000663 AC: 1AN: 150762Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248446Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134774
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460052Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726284
GnomAD4 genome ? AF: 0.00000663 AC: 1AN: 150762Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73614
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Pathogenic:3
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
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 | - | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2023 | Reported heterozygous with another variant in the DYNC2H1 gene, phase unknown, in an individual with a skeletal ciliopathy (Zhang et al., 2018) Zhang W et al. (2018) Hum Mutat 39 (1):152-166 (PMID: 29068549); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29068549) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at