21-37481287-A-C

Position:

• chr21-37481287-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347721.2(DYRK1A):​c.489+461A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,488 control chromosomes in the GnomAD database, including 6,559 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 0.29 (6545 hom., cov: 32)
  • Exomes 𝑓: 0.27 (14 hom.)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.489+461A>C		intron_variant		ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2	c.489+461A>C		intron_variant			NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44058 AN: 151882 Hom.: 6540 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.270 AC: 132 AN: 488 Hom.: 14 Cov.: 0 AF XY: 0.264 AC XY: 75 AN XY: 284

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.290 AC: 44093 AN: 152000 Hom.: 6545 Cov.: 32 AF XY: 0.294 AC XY: 21846 AN XY: 74312

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.295

Alfa AF: 0.251 Hom.: 2106

Bravo AF: 0.283

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs11701810; hg19: chr21-38853589;