chr13-26254730-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_001260.3(CDK8):c.89G>A(p.Gly30Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G30S) has been classified as Pathogenic.
Frequency
Consequence
NM_001260.3 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK8 | NM_001260.3 | c.89G>A | p.Gly30Asp | missense_variant | 1/13 | ENST00000381527.8 | |
CDK8 | NM_001318368.2 | c.89G>A | p.Gly30Asp | missense_variant | 1/13 | ||
CDK8 | NM_001346501.2 | c.-373G>A | 5_prime_UTR_variant | 1/12 | |||
CDK8 | XM_047430033.1 | c.-142G>A | 5_prime_UTR_variant | 1/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK8 | ENST00000381527.8 | c.89G>A | p.Gly30Asp | missense_variant | 1/13 | 1 | NM_001260.3 | P1 | |
CDK8 | ENST00000536792.5 | c.89G>A | p.Gly30Asp | missense_variant, NMD_transcript_variant | 1/12 | 1 | |||
CDK8 | ENST00000700501.1 | c.89G>A | p.Gly30Asp | missense_variant, NMD_transcript_variant | 1/12 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Intellectual developmental disorder with hypotonia and behavioral abnormalities Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | Feb 23, 2023 | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.72). Different missense changes at the same codon (p.Gly30Cys, p.Gly30Ser) have been reported to be associated with CDK8 related disorder (ClinVar ID: VCV000805983, VCV000871513 / PMID: 30905399). However the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.