rs1803439

Variant names:

• chr21-37513139-A-G
• rs1803439
• NM_001347721.2:c.*608A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 8 publications found

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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347721.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1A	NM_001347721.2	MANE Select	c.*608A>G		3_prime_UTR	Exon 12 of 12	NP_001334650.1	Q13627-2
	DYRK1A	NM_001396.5		c.*608A>G		3_prime_UTR	Exon 12 of 12	NP_001387.2
	DYRK1A	NM_001347722.2		c.*608A>G		3_prime_UTR	Exon 12 of 12	NP_001334651.1	Q13627-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1A	ENST00000647188.2	MANE Select	c.*608A>G		3_prime_UTR	Exon 12 of 12	ENSP00000494572.1	Q13627-2
	DYRK1A	ENST00000338785.8	TSL:1	c.*1276A>G		3_prime_UTR	Exon 13 of 13	ENSP00000342690.3	Q13627-5
	DYRK1A	ENST00000865096.1		c.*608A>G		3_prime_UTR	Exon 12 of 12	ENSP00000535155.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50457 AN: 151782 Hom.: 8500 Cov.: 30

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.: 83 Cov.: 0 AF XY: 0.304 AC XY: 245 AN XY: 806

African (AFR) AF: 0.200 AC: 2 AN: 10

American (AMR) AF: 0.328 AC: 42 AN: 128

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.214 AC: 3 AN: 14

South Asian (SAS) AF: 0.400 AC: 20 AN: 50

European-Finnish (FIN) AF: 0.370 AC: 159 AN: 430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.305 AC: 215 AN: 706

Other (OTH) AF: 0.375 AC: 12 AN: 32

GnomAD4 genome AF: 0.332 AC: 50487 AN: 151900 Hom.: 8506 Cov.: 30 AF XY: 0.336 AC XY: 24940 AN XY: 74246

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: 72 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23487 AN: 67936

Other (OTH) AF: 0.339 AC: 715 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.5
DANN	Benign	0.74
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1803439; hg19: chr21-38885442; COSMIC: COSV58705498; COSMIC: COSV58705498;