NM_001347721.2:c.-76-211delT

Variant names:

• chr21-37420078-GT-G
• rs140342279
• NM_001347721.2:c.-76-211delT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001347721.2(DYRK1A):​c.-76-211delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 223,470 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: DYRK1A NM_001347721.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 37 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1A	NM_001347721.2	c.-76-211delT		intron_variant	Intron 1 of 11	ENST00000647188.2	NP_001334650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2	c.-76-211delT		intron_variant	Intron 1 of 11		NM_001347721.2	ENSP00000494572.1

Frequencies

GnomAD3 genomes AF: 0.000245 AC: 36 AN: 146908 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000604

Gnomad OTH AF: 0.000497

GnomAD4 exome AF: 0.00186 AC: 142 AN: 76482 Hom.: 0 Cov.: 0 AF XY: 0.00192 AC XY: 75 AN XY: 39016

Gnomad4 AFR exome AF: 0.00234

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00210

Gnomad4 EAS exome AF: 0.00130

Gnomad4 SAS exome AF: 0.00363

Gnomad4 FIN exome AF: 0.00146

Gnomad4 NFE exome AF: 0.00189

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.000252 AC: 37 AN: 146988 Hom.: 0 Cov.: 32 AF XY: 0.000265 AC XY: 19 AN XY: 71586

Gnomad4 AFR AF: 0.000749

Gnomad4 AMR AF: 0.000135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000604

Gnomad4 OTH AF: 0.000493

Bravo AF: 0.000276

ClinVar

Not reported in ClinVar

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;