chr21-37410609-T-C

Position:

• chr21-37410609-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_101395.2(DYRK1A):​c.-138T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,080 control chromosomes in the GnomAD database, including 24,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24445 hom., cov: 33)
  • Exomes 𝑓: 0.67 (6 hom.)
• Consequence: DYRK1A NM_101395.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 21-37410609-T-C is Benign according to our data. Variant chr21-37410609-T-C is described in ClinVar as [Benign]. Clinvar id is 1236621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.-76-9690T>C		intron_variant		ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2	c.-76-9690T>C		intron_variant			NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84727 AN: 151938 Hom.: 24409 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.667 AC: 16 AN: 24 Hom.: 6 Cov.: 0 AF XY: 0.650 AC XY: 13 AN XY: 20

Gnomad4 NFE exome AF: 0.611

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.558 AC: 84823 AN: 152056 Hom.: 24445 Cov.: 33 AF XY: 0.553 AC XY: 41108 AN XY: 74296

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.576

Alfa AF: 0.545 Hom.: 2906

Bravo AF: 0.561

Asia WGS AF: 0.513 AC: 1785 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9981736; hg19: chr21-38782911;