chr17-46171276-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 16P and 4B. PVS1PP5_Very_StrongBS2
The NM_015443.4(KANSL1):c.868C>T(p.Arg290*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000291 in 1,613,986 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 (★★). 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.868C>T | p.Arg290* | stop_gained | Exon 2 of 15 | ENST00000432791.7 | NP_056258.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152102Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251448Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135896
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727248
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152102Hom.: 0 Cov.: 35 AF XY: 0.0000808 AC XY: 6AN XY: 74296
ClinVar
Submissions by phenotype
not provided Pathogenic:2
KANSL1: PVS1, PS2, BS2 -
Identified in an individual from a developmental delay cohort in the published literature (Wang et al., 2020); 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; This variant is associated with the following publications: (PMID: 33004838) -
Koolen-de Vries syndrome Pathogenic:2
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This variant was identified in a 12 year old female with a history of intellectual disability, hypotonia, short stature, atrial septal defect, patent ductus arteriosus, multicystic dysplastic left kidney, congenital valgus foot deformity, constipation, and dysphagia. Dysmorphic facial features include coarse facies, hypertelorism, epicanthal folds, broad nasal tip, and wide spaced teeth. The variant is present in the gnomAD Finnish population at 0.058% but is absent from all other populations with sufficient data. The presence of an inversion polymorphism at 17q21.31 which overlaps KANSL1 complicates the interpretation of this variant. The proband is adopted and parental samples were not available. However, there was very strong clinical correlation between this patient's clinical features and Koolen-DeVries syndrome. In addition, whole exome sequencing identified an additional VUS in a gene of uncertain significance. -
Inborn genetic diseases Pathogenic:1
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not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at