rs1057175147

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_001347721.2(DYRK1A):c.47G>A(p.Arg16Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DYRK1A
NM_001347721.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.60

Publications

0 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), G2P

DYRK1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31274283).

BP6

Variant 21-37472720-G-A is Benign according to our data. Variant chr21-37472720-G-A is described in ClinVar as Benign. ClinVar VariationId is 472252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1A	NM_001347721.2 link	c.47G>A	p.Arg16Gln	missense_variant	Exon 3 of 12	ENST00000647188.2	NP_001334650.1	Q13627-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1A	ENST00000647188.2 link	c.47G>A	p.Arg16Gln	missense_variant	Exon 3 of 12		NM_001347721.2	ENSP00000494572.1		Q13627-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456464

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33326

American (AMR)

AF:

0.00

AC:

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.00

AC:

AN:

85680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1108388

Other (OTH)

AF:

0.00

AC:

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DYRK1A-related intellectual disability syndrome

Benign:1

Oct 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

.;.;T;.;.;.;.;T;T;T;.;.;.;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;.;.;.;D;.;D;D;.;D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.31

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.0

.;L;L;L;L;L;.;.;L;L;L;L;.;L

PhyloP100

9.6

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.42

.;.;.;.;N;.;.;N;N;N;.;.;.;N

REVEL

Benign

0.23

Sift

Pathogenic

0.0

.;.;.;.;D;.;.;D;D;D;.;.;.;D

Sift4G

Benign

0.37

.;.;.;.;T;.;.;T;T;T;.;.;.;T

Polyphen

0.086, 0.052

.;B;B;B;B;B;.;.;B;B;B;B;.;B

Vest4

0.63, 0.66, 0.68, 0.63

MutPred

0.15

Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);Loss of phosphorylation at S14 (P = 0.0831);.;Loss of phosphorylation at S14 (P = 0.0831);

MVP

0.73

MPC

1.7

ClinPred

0.88

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.52

gMVP

0.45

Mutation Taster

=68/32

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over