dbSNP rs1803439: DYRK1A:c.*608A>G (chr21-37513139-A-G) – 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.*608A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 153,272 control chromosomes in the GnomAD database, including 8,589 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 0.33 ( 8506 hom., cov: 30)

Exomes 𝑓: 0.33 ( 83 hom. )

Consequence

DYRK1A
NM_001347721.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.00

Publications

8 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=-0.62).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1A	NM_001347721.2 link	c.*608A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2 link	c.*608A>G		3_prime_UTR_variant	Exon 12 of 12		NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50457

AN:

151782

Hom.:

8500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.330

AC:

453

AN:

1372

Hom.:

Cov.:

AF XY:

0.304

AC XY:

245

AN XY:

806

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.328

AC:

AN:

128

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.214

AC:

AN:

South Asian (SAS)

AF:

0.400

AC:

AN:

European-Finnish (FIN)

AF:

0.370

AC:

159

AN:

430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.305

AC:

215

AN:

706

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.332

AC:

50487

AN:

151900

Hom.:

8506

Cov.:

AF XY:

0.336

AC XY:

24940

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.296

AC:

12269

AN:

41424

American (AMR)

AF:

0.326

AC:

4973

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

891

AN:

3466

East Asian (EAS)

AF:

0.361

AC:

1857

AN:

5150

South Asian (SAS)

AF:

0.419

AC:

2012

AN:

4802

European-Finnish (FIN)

AF:

0.382

AC:

4028

AN:

10534

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23487

AN:

67936

Other (OTH)

AF:

0.339

AC:

715

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1679

3358

5038

6717

8396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.345

Hom.:

8431

Bravo

AF:

0.329

Asia WGS

AF:

0.404

AC:

1402

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.5

(source)

DANN

Benign

0.74

PhyloP100

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over