chr21-37420484-TGGG-T

Variant names:

• chr21-37420484-TGGG-T
• rs143066663
• NM_001347721.2:c.10+104_10+106delGGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001347721.2(DYRK1A):​c.10+104_10+106delGGG 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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• DYRK1A-related intellectual disability syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1268823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347721.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1A	NM_001347721.2	MANE Select	c.10+104_10+106delGGG		intron	N/A	NP_001334650.1	Q13627-2
	DYRK1A	NM_001396.5		c.10+104_10+106delGGG		intron	N/A	NP_001387.2
	DYRK1A	NM_001347722.2		c.10+104_10+106delGGG		intron	N/A	NP_001334651.1	Q13627-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1A	ENST00000647188.2	MANE Select	c.10+101_10+103delGGG		intron	N/A	ENSP00000494572.1	Q13627-2
	DYRK1A	ENST00000398960.7	TSL:1	c.10+101_10+103delGGG		intron	N/A	ENSP00000381932.2	Q13627-1
	DYRK1A	ENST00000338785.8	TSL:1	c.10+101_10+103delGGG		intron	N/A	ENSP00000342690.3	Q13627-5

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

African (AFR) AF: 0.0158 AC: 392 AN: 24762

American (AMR) AF: 0.0390 AC: 1552 AN: 39822

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 1076 AN: 22658

East Asian (EAS) AF: 0.000219 AC: 8 AN: 36558

South Asian (SAS) AF: 0.0180 AC: 1342 AN: 74478

European-Finnish (FIN) AF: 0.148 AC: 7619 AN: 51318

Middle Eastern (MID) AF: 0.00958 AC: 47 AN: 4904

European-Non Finnish (NFE) AF: 0.106 AC: 79693 AN: 751162

Other (OTH) AF: 0.0812 AC: 3776 AN: 46476

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

African (AFR) AF: 0.0188 AC: 782 AN: 41522

American (AMR) AF: 0.0569 AC: 868 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10576

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7570 AN: 67930

Other (OTH) AF: 0.0664 AC: 140 AN: 2108

Alfa AF: 0.100 Hom.: 111

Bravo AF: 0.0667

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs143066663; hg19: chr21-38792786;