rs2835773

Variant names:

• chr21-37493662-A-G
• rs2835773
• NM_001347721.2:c.1071+499A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-37493662-A-G
• chr21-37493662-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347721.2(DYRK1A):​c.1071+499A>G 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 151,934 control chromosomes in the GnomAD database, including 15,939 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 (15939 hom., cov: 31)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 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.1071+499A>G		intron	N/A	NP_001334650.1	Q13627-2
	DYRK1A	NM_001396.5		c.1098+499A>G		intron	N/A	NP_001387.2
	DYRK1A	NM_001347722.2		c.1071+499A>G		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.1071+499A>G		intron	N/A	ENSP00000494572.1	Q13627-2
	DYRK1A	ENST00000398960.7	TSL:1	c.1098+499A>G		intron	N/A	ENSP00000381932.2	Q13627-1
	DYRK1A	ENST00000338785.8	TSL:1	c.1098+499A>G		intron	N/A	ENSP00000342690.3	Q13627-5

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67789 AN: 151816 Hom.: 15935 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.446 AC: 67815 AN: 151934 Hom.: 15939 Cov.: 31 AF XY: 0.451 AC XY: 33463 AN XY: 74270

African (AFR) AF: 0.293 AC: 12131 AN: 41398

American (AMR) AF: 0.533 AC: 8132 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2940 AN: 5168

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4816

European-Finnish (FIN) AF: 0.492 AC: 5198 AN: 10564

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33929 AN: 67940

Other (OTH) AF: 0.427 AC: 900 AN: 2106

Alfa AF: 0.460 Hom.: 2092

Bravo AF: 0.444

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.75
PhyloP100		-2.0
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: rs2835773; hg19: chr21-38865964;