chr21-37420078-G-GT

Position:

• chr21-37420078-G-GT

Variant summary

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

The NM_130436.2(DYRK1A):​c.-287dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 219,690 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (7 hom., cov: 32)
  • Exomes 𝑓: 0.052 (0 hom.)
• Consequence: DYRK1A NM_130436.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412

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 21-37420078-G-GT is Benign according to our data. Variant chr21-37420078-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 1201294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.-76-211dupT		intron_variant		ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2	c.-76-211dupT		intron_variant			NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.00659 AC: 968 AN: 146840 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00249

GnomAD4 exome AF: 0.0518 AC: 3768 AN: 72770 Hom.: 0 Cov.: 0 AF XY: 0.0531 AC XY: 1970 AN XY: 37102

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.0465

Gnomad4 EAS exome AF: 0.0468

Gnomad4 SAS exome AF: 0.0418

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.0535

Gnomad4 OTH exome AF: 0.0505

GnomAD4 genome AF: 0.00659 AC: 968 AN: 146920 Hom.: 7 Cov.: 32 AF XY: 0.00654 AC XY: 468 AN XY: 71544

Gnomad4 AFR AF: 0.00177

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00247

Bravo AF: 0.00499

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

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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: rs140342279; hg19: chr21-38792380;