21-37472046-T-C

Position:

• chr21-37472046-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.11-638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,242 control chromosomes in the GnomAD database, including 59,650 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 0.88 (59650 hom., cov: 32)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.11-638T>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.11-638T>C		intron_variant			NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134364 AN: 152124 Hom.: 59595 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.867

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.883 AC: 134479 AN: 152242 Hom.: 59650 Cov.: 32 AF XY: 0.885 AC XY: 65899 AN XY: 74436

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.869

Alfa AF: 0.871 Hom.: 6743

Bravo AF: 0.891

Asia WGS AF: 0.943 AC: 3282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.45

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: rs2835761; hg19: chr21-38844348;