Variant chr21-37420484-TGGG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.294

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
DYRK1A	NM_001347721.2 linkuse as main transcript	c.10+104_10+106delGGG		intron_variant		ENST00000647188.2	NP_001334650.1	Q13627-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2 linkuse as main transcript	c.10+104_10+106delGGG		intron_variant			NM_001347721.2	ENSP00000494572.1		Q13627-2

Frequencies

GnomAD3 genomes

AF:

0.0753

AC:

11443

AN:

151956

Hom.:

630

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0756

AC XY:

5620

AN XY:

74342

show subpopulations

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:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over