Genetic Variant DYRK1A:c.10+25126G>A (chr21-37445510-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001347721.2(DYRK1A):c.10+25126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,222 control chromosomes in the GnomAD database, including 1,423 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 0.13 ( 1423 hom., cov: 32)

Consequence

DYRK1A
NM_001347721.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58

Publications

5 publications found

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]

DYRK1A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
DYRK1A-related intellectual disability syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

DYRK1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1A	NM_001347721.2 link	c.10+25126G>A		intron_variant	Intron 2 of 11	ENST00000647188.2	NP_001334650.1	Q13627-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2 link	c.10+25126G>A		intron_variant	Intron 2 of 11		NM_001347721.2	ENSP00000494572.1		Q13627-2

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19963

AN:

152104

Hom.:

1419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.0898

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.0793

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.131

AC:

19983

AN:

152222

Hom.:

1423

Cov.:

AF XY:

0.133

AC XY:

9887

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.132

AC:

5459

AN:

41512

American (AMR)

AF:

0.0896

AC:

1372

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3472

East Asian (EAS)

AF:

0.0337

AC:

175

AN:

5192

South Asian (SAS)

AF:

0.0787

AC:

379

AN:

4816

European-Finnish (FIN)

AF:

0.220

AC:

2331

AN:

10592

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9614

AN:

68018

Other (OTH)

AF:

0.121

AC:

256

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

893

1785

2678

3570

4463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.134

Hom.:

2507

Bravo

AF:

0.120

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.039

(source)

DANN

Benign

0.40

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over