rs8132976

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001347721.2(DYRK1A):​c.1212+4490C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,552 control chromosomes in the GnomAD database, including 23,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23150 hom., cov: 31)

Consequence

DYRK1A
NM_001347721.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0110
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DYRK1ANM_001347721.2 linkuse as main transcriptc.1212+4490C>A intron_variant ENST00000647188.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DYRK1AENST00000647188.2 linkuse as main transcriptc.1212+4490C>A intron_variant NM_001347721.2 P1Q13627-2

Frequencies

GnomAD3 genomes
AF:
0.546
AC:
82627
AN:
151432
Hom.:
23117
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.674
Gnomad AMI
AF:
0.388
Gnomad AMR
AF:
0.470
Gnomad ASJ
AF:
0.498
Gnomad EAS
AF:
0.435
Gnomad SAS
AF:
0.549
Gnomad FIN
AF:
0.510
Gnomad MID
AF:
0.542
Gnomad NFE
AF:
0.502
Gnomad OTH
AF:
0.563
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.546
AC:
82715
AN:
151552
Hom.:
23150
Cov.:
31
AF XY:
0.541
AC XY:
40121
AN XY:
74100
show subpopulations
Gnomad4 AFR
AF:
0.675
Gnomad4 AMR
AF:
0.470
Gnomad4 ASJ
AF:
0.498
Gnomad4 EAS
AF:
0.433
Gnomad4 SAS
AF:
0.549
Gnomad4 FIN
AF:
0.510
Gnomad4 NFE
AF:
0.502
Gnomad4 OTH
AF:
0.565
Alfa
AF:
0.536
Hom.:
2783
Bravo
AF:
0.547
Asia WGS
AF:
0.512
AC:
1762
AN:
3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.94
DANN
Benign
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8132976; hg19: chr21-38873051; API