21-37367544-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.174

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
DYRK1A	NM_001347721.2	c.-161C>T		5_prime_UTR_variant	1/12	ENST00000647188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYRK1A	ENST00000647188.2	c.-161C>T		5_prime_UTR_variant	1/12		NM_001347721.2	P1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 8785 AN: 146338 Hom.: 300 Cov.: 32

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: 34 AN: 612 Hom.: 1 Cov.: 0 AF XY: 0.0515 AC XY: 21 AN XY: 408

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.: 32 AF XY: 0.0587 AC XY: 4193 AN XY: 71378

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.: 23

Asia WGS AF: 0.0570 AC: 171 AN: 2978

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	18
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

Other links and lift over

dbSNP: rs28565161; hg19: chr21-38739846;