chr21-37487125-T-C

Position:

• chr21-37487125-T-C

Variant summary

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

The NM_001347721.2(DYRK1A):​c.637+511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,952 control chromosomes in the GnomAD database, including 15,909 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 0.45 (15909 hom., cov: 31)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.637+511T>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.637+511T>C		intron_variant			NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67726 AN: 151826 Hom.: 15905 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.446 AC: 67752 AN: 151944 Hom.: 15909 Cov.: 31 AF XY: 0.450 AC XY: 33428 AN XY: 74276

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.429

Alfa AF: 0.454 Hom.: 4516

Bravo AF: 0.444

Asia WGS AF: 0.480 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.75

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: rs1024294; hg19: chr21-38859427;