rs281865469
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015443.4(KANSL1):c.1816C>T(p.Arg606Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R606R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_015443.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.1816C>T | p.Arg606Ter | stop_gained | 6/15 | ENST00000432791.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KANSL1 | ENST00000432791.7 | c.1816C>T | p.Arg606Ter | stop_gained | 6/15 | 1 | NM_015443.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461296Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726920
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Koolen-de Vries syndrome Pathogenic:3Other:1
Pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Jun 05, 2019 | This variant is interpreted as a Pathogenic for Koolen-De Vries syndrome, autosomal dominant. The following ACMG Tag(s) were applied: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6: Assumed de novo, but without confirmation of paternity and maternity. PVS1: Predicted nullvariant in a gene where LOF is a known mechanism of disease. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 29, 2012 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2022 | This sequence change creates a premature translational stop signal (p.Arg606*) in the KANSL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KANSL1 are known to be pathogenic (PMID: 22544363, 22544367). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Koolen-de Vries syndrome (PMID: 22544367). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 31693). For these reasons, this variant has been classified as Pathogenic. - |
Global developmental delay Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Génétique des Maladies du Développement, Hospices Civils de Lyon | Nov 01, 2019 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 20, 2021 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22544367, 26293599) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at