chr21-37420150-T-TTAAG

Position:

• chr21-37420150-T-TTAAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001347721.2(DYRK1A):​c.-76-147_-76-144dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 363,756 control chromosomes in the GnomAD database, including 1,644 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (627 hom., cov: 31)
  • Exomes 𝑓: 0.084 (1017 hom.)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.877

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 -10 ACMG points.

• BP6: Variant 21-37420150-T-TTAAG is Benign according to our data. Variant chr21-37420150-T-TTAAG is described in ClinVar as [Benign]. Clinvar id is 1261606.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
DYRK1A	NM_001347721.2	c.-76-147_-76-144dup		intron_variant		ENST00000647188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYRK1A	ENST00000647188.2	c.-76-147_-76-144dup		intron_variant			NM_001347721.2	P1

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11436 AN: 152050 Hom.: 627 Cov.: 31

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0672

GnomAD4 exome AF: 0.0838 AC: 17734 AN: 211588 Hom.: 1017 Cov.: 3 AF XY: 0.0839 AC XY: 9146 AN XY: 108970

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.0433

Gnomad4 ASJ exome AF: 0.0434

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.0134

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0757

GnomAD4 genome AF: 0.0751 AC: 11433 AN: 152168 Hom.: 627 Cov.: 31 AF XY: 0.0753 AC XY: 5604 AN XY: 74376

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0665

Alfa AF: 0.0997 Hom.: 106

Bravo AF: 0.0665

Asia WGS AF: 0.0100 AC: 37 AN: 3478

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

Jul 05, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138013864; hg19: chr21-38792452;