21-37420484-TGGG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001347721.2(DYRK1A):c.10+104_10+106del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,204,212 control chromosomes in the GnomAD database, including 6,086 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (630 hom., cov: 31)
  • Exomes 𝑓: 0.091 (5456 hom.)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.294

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 -10 ACMG points.

• BP6: Variant 21-37420484-TGGG-T is Benign according to our data. Variant chr21-37420484-TGGG-T is described in ClinVar as [Benign]. Clinvar id is 1268823.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-37420484-TGGG-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYRK1A	NM_001347721.2	c.10+104_10+106del		intron_variant		ENST00000647188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYRK1A	ENST00000647188.2	c.10+104_10+106del		intron_variant			NM_001347721.2	P1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11443 AN: 151956 Hom.: 630 Cov.: 31

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0671

GnomAD4 exome AF: 0.0908 AC: 95505 AN: 1052138 Hom.: 5456 AF XY: 0.0884 AC XY: 47722 AN XY: 539796

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.0390

Gnomad4 ASJ exome AF: 0.0475

Gnomad4 EAS exome AF: 0.000219

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0812

GnomAD4 genome AF: 0.0752 AC: 11440 AN: 152074 Hom.: 630 Cov.: 31 AF XY: 0.0756 AC XY: 5620 AN XY: 74342

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.100 Hom.: 111

Bravo AF: 0.0667

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs143066663; hg19: chr21-38792786;