rs150200258

Variant names:

• chr21-37480685-C-G
• rs150200258
• NM_001347721.2:c.348C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-37480685-C-G
• chr21-37480685-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001347721.2(DYRK1A):​c.348C>G​(p.Asp116Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. D116D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYRK1A NM_001347721.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

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]

DYRK1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• DYRK1A-related intellectual disability syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000309268 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06230691).
• BP6: Variant 21-37480685-C-G is Benign according to our data. Variant chr21-37480685-C-G is described in ClinVar as Benign. ClinVar VariationId is 1354837.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347721.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1A	NM_001347721.2	MANE Select	c.348C>G	p.Asp116Glu	missense	Exon 5 of 12	NP_001334650.1	Q13627-2
	DYRK1A	NM_001396.5		c.375C>G	p.Asp125Glu	missense	Exon 5 of 12	NP_001387.2
	DYRK1A	NM_001347722.2		c.348C>G	p.Asp116Glu	missense	Exon 5 of 12	NP_001334651.1	Q13627-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1A	ENST00000647188.2	MANE Select	c.348C>G	p.Asp116Glu	missense	Exon 5 of 12	ENSP00000494572.1	Q13627-2
	DYRK1A	ENST00000398960.7	TSL:1	c.375C>G	p.Asp125Glu	missense	Exon 5 of 12	ENSP00000381932.2	Q13627-1
	DYRK1A	ENST00000338785.8	TSL:1	c.375C>G	p.Asp125Glu	missense	Exon 6 of 13	ENSP00000342690.3	Q13627-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	DYRK1A-related intellectual disability syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.2	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.13
Sift	Benign	0.91	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.14		Loss of MoRF binding (P = 0.1306)
MVP		0.41
MPC		1.0
ClinPred		0.80	D
GERP RS		4.1
Varity_R		0.073
gMVP		0.10
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150200258; hg19: chr21-38852987;