Variant 21-37367544-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001347721.2(DYRK1A):c.-161C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 147,050 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 304 hom., cov: 32)

Exomes 𝑓: 0.056 ( 1 hom. )

Consequence

DYRK1A
NM_001347721.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.174

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 21-37367544-C-T is Benign according to our data. Variant chr21-37367544-C-T is described in ClinVar as [Benign]. Clinvar id is 1296230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0598 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.-161C>T		5_prime_UTR_variant	1/12	ENST00000647188.2	NP_001334650.1	Q13627-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/12		NM_001347721.2	ENSP00000494572.1		Q13627-2

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

8785

AN:

146338

Hom.:

300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.00449

Gnomad AMR

AF:

0.0597

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0650

Gnomad SAS

AF:

0.0420

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.141

Gnomad NFE

AF:

0.0589

Gnomad OTH

AF:

0.0832

GnomAD4 exome

AF:

0.0556

AC:

AN:

612

Hom.:

Cov.:

AF XY:

0.0515

AC XY:

AN XY:

408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0601

AC:

8798

AN:

146438

Hom.:

304

Cov.:

AF XY:

0.0587

AC XY:

4193

AN XY:

71378

show subpopulations

Gnomad4 AFR

AF:

0.0619

Gnomad4 AMR

AF:

0.0594

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0650

Gnomad4 SAS

AF:

0.0420

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0589

Gnomad4 OTH

AF:

0.0823

Alfa

AF:

0.0521

Hom.:

Asia WGS

AF:

0.0570

AC:

171

AN:

2978

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.5

Splicing

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