21-37513139-A-G

Position:

• chr21-37513139-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.*608A>G		3_prime_UTR_variant	12/12	ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2	c.*608A>G		3_prime_UTR_variant	12/12		NM_001347721.2	ENSP00000494572.1
DYRK1A	ENST00000338785.8	c.*1276A>G		3_prime_UTR_variant	13/13	1		ENSP00000342690.3
DYRK1A	ENST00000646548.1	c.*608A>G		3_prime_UTR_variant	11/11			ENSP00000495908.1
DYRK1A	ENST00000647504.1	c.*608A>G		3_prime_UTR_variant	11/11			ENSP00000495571.1

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.328

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.375

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.339

Alfa AF: 0.344 Hom.: 5240

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
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

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