rs887440216
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001347721.2(DYRK1A):c.2216C>A(p.Ser739Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
DYRK1A
NM_001347721.2 missense
NM_001347721.2 missense
Scores
5
11
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.75
Genes affected
DYRK1A (HGNC:3091): (dual specificity tyrosine phosphorylation regulated kinase 1A) This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene. It is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the DYRK1A gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 31 curated pathogenic missense variants (we use a threshold of 10). The gene has 88 curated benign missense variants. Gene score misZ: 3.3441 (above the threshold of 3.09). Trascript score misZ: 4.1103 (above the threshold of 3.09). GenCC associations: The gene is linked to complex neurodevelopmental disorder, DYRK1A-related intellectual disability syndrome.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;.;.;D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;.;.;.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;N;.;.;N;N;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;.;.;.;D;.;.
REVEL
Uncertain
Sift
Pathogenic
.;.;.;.;.;D;.;.
Sift4G
Pathogenic
.;.;.;.;.;D;.;.
Polyphen
D;.;D;D;D;D;D;D
Vest4
0.75
MutPred
0.19
.;.;Loss of disorder (P = 0.0076);.;.;Loss of disorder (P = 0.0076);Loss of disorder (P = 0.0076);.;
MVP
0.77
MPC
0.76
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at