Genetic Variant DYRK1B:p.Pro614Thr (chr19-39825765-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004714.3(DYRK1B):c.1840C>A(p.Pro614Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,570,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

DYRK1B
NM_004714.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.24

Publications

0 publications found

Variant links:

Genes affected

DYRK1B (HGNC:3092): (dual specificity tyrosine phosphorylation regulated kinase 1B) This gene encodes a member of a family of nuclear-localized protein kinases. The encoded protein participates in the regulation of the cell cycle. Expression of this gene may be altered in tumor cells, and mutations in this gene were found to cause abdominal obesity-metabolic syndrome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DYRK1B Gene-Disease associations (from GenCC):

abdominal obesity-metabolic syndrome 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

DYRK1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031339288).

BS2

High AC in GnomAd4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYRK1B	NM_004714.3	MANE Select	c.1840C>A	p.Pro614Thr	missense	Exon 11 of 11	NP_004705.1	Q9Y463-1
DYRK1B	NM_006484.3		c.1756C>A	p.Pro586Thr	missense	Exon 12 of 12	NP_006475.1	Q9Y463-3
DYRK1B	NM_006483.3		c.1720C>A	p.Pro574Thr	missense	Exon 11 of 11	NP_006474.1	Q9Y463-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYRK1B	ENST00000323039.10	TSL:1 MANE Select	c.1840C>A	p.Pro614Thr	missense	Exon 11 of 11	ENSP00000312789.4	Q9Y463-1
DYRK1B	ENST00000593685.5	TSL:5	c.2020C>A	p.Pro674Thr	missense	Exon 11 of 11	ENSP00000469863.2	A0A9H4CVU7
DYRK1B	ENST00000348817.7	TSL:5	c.1756C>A	p.Pro586Thr	missense	Exon 12 of 12	ENSP00000221803.4	Q9Y463-3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000180

AC:

AN:

172096

AF XY:

0.000245

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000609

Gnomad NFE exome

AF:

0.000402

Gnomad OTH exome

AF:

0.000216

GnomAD4 exome

AF:

0.000245

AC:

348

AN:

1418334

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

181

AN XY:

701858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32374

American (AMR)

AF:

0.0000537

AC:

AN:

37236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25420

East Asian (EAS)

AF:

0.00

AC:

AN:

36928

South Asian (SAS)

AF:

0.00

AC:

AN:

81778

European-Finnish (FIN)

AF:

0.0000200

AC:

AN:

49896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5170

European-Non Finnish (NFE)

AF:

0.000308

AC:

336

AN:

1090746

Other (OTH)

AF:

0.000153

AC:

AN:

58786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.000125

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41400

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000185

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.000179

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DYRK1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Benign

-0.20

Eigen_PC

Benign

0.0044

FATHMM_MKL

Benign

0.68

M_CAP

Benign

0.013

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

1.2

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.12

REVEL

Benign

0.049

Sift

Uncertain

0.015

Sift4G

Benign

0.66

Polyphen

0.020

Vest4

0.18

MVP

0.51

MPC

0.56

ClinPred

0.073

GERP RS

5.0

Varity_R

0.12

gMVP

0.24

Mutation Taster

=80/20

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over