rs11701810

Variant names:

• chr21-37481287-A-C
• rs11701810
• ENST00000462274.2:n.871A>C

Your query was ambiguous. Multiple possible variants found:

• chr21-37481287-A-C
• chr21-37481287-A-G
• chr21-37481287-A-T

Variant summary

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

The ENST00000462274.2(DYRK1A):​n.871A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,488 control chromosomes in the GnomAD database, including 6,559 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 0.29 (6545 hom., cov: 32)
  • Exomes 𝑓: 0.27 (14 hom.)
• Consequence: DYRK1A ENST00000462274.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P

ENSG00000309268 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.489+461A>C		intron_variant	Intron 5 of 11	ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2	c.489+461A>C		intron_variant	Intron 5 of 11		NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44058 AN: 151882 Hom.: 6540 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.270 AC: 132 AN: 488 Hom.: 14 Cov.: 0 AF XY: 0.264 AC XY: 75 AN XY: 284

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.400 AC: 8 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.500 AC: 3 AN: 6

South Asian (SAS) AF: 0.500 AC: 4 AN: 8

European-Finnish (FIN) AF: 0.313 AC: 5 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.254 AC: 101 AN: 398

Other (OTH) AF: 0.308 AC: 8 AN: 26

GnomAD4 genome AF: 0.290 AC: 44093 AN: 152000 Hom.: 6545 Cov.: 32 AF XY: 0.294 AC XY: 21846 AN XY: 74312

African (AFR) AF: 0.271 AC: 11235 AN: 41432

American (AMR) AF: 0.265 AC: 4046 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1870 AN: 5152

South Asian (SAS) AF: 0.400 AC: 1925 AN: 4818

European-Finnish (FIN) AF: 0.341 AC: 3607 AN: 10572

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19708 AN: 67942

Other (OTH) AF: 0.295 AC: 625 AN: 2116

Alfa AF: 0.258 Hom.: 2633

Bravo AF: 0.283

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.72
PhyloP100		-0.31
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: rs11701810; hg19: chr21-38853589;