rs587777097
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_052844.4(DYNC2I2):c.472C>T(p.Gln158Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000136 in 1,613,322 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. Q158Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_052844.4 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 |
---|---|---|---|---|---|---|---|
DYNC2I2 | NM_052844.4 | c.472C>T | p.Gln158Ter | stop_gained | 3/9 | ENST00000372715.7 | |
DYNC2I2 | XM_047424057.1 | c.472C>T | p.Gln158Ter | stop_gained | 4/10 | ||
DYNC2I2 | XM_011519179.3 | c.472C>T | p.Gln158Ter | stop_gained | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2I2 | ENST00000372715.7 | c.472C>T | p.Gln158Ter | stop_gained | 3/9 | 1 | NM_052844.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249596Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135270
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461120Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 726892
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Short-rib thoracic dysplasia 11 with or without polydactyly Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2022 | This sequence change creates a premature translational stop signal (p.Gln158*) in the WDR34 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR34 are known to be pathogenic (PMID: 24183449, 24183451, 28379358). This variant is present in population databases (rs587777097, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with Jeune asphyxiating thoracic dysplasia (PMID: 24183451). ClinVar contains an entry for this variant (Variation ID: 97044). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at