NM_004714.3:c.1784G>A

Variant names:

• chr19-39825821-C-T
• rs200681061
• NM_004714.3:c.1784G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_004714.3(DYRK1B):​c.1784G>A​(p.Arg595Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,607,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R595W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: DYRK1B NM_004714.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.21
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014856786).
• BP6: Variant 19-39825821-C-T is Benign according to our data. Variant chr19-39825821-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3035214.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 36 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	NM_004714.3	MANE Select	c.1784G>A	p.Arg595Gln	missense	Exon 11 of 11	NP_004705.1	Q9Y463-1
	DYRK1B	NM_006484.3		c.1700G>A	p.Arg567Gln	missense	Exon 12 of 12	NP_006475.1	Q9Y463-3
	DYRK1B	NM_006483.3		c.1664G>A	p.Arg555Gln	missense	Exon 11 of 11	NP_006474.1	Q9Y463-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	ENST00000323039.10	TSL:1 MANE Select	c.1784G>A	p.Arg595Gln	missense	Exon 11 of 11	ENSP00000312789.4	Q9Y463-1
	DYRK1B	ENST00000593685.5	TSL:5	c.1964G>A	p.Arg655Gln	missense	Exon 11 of 11	ENSP00000469863.2	A0A9H4CVU7
	DYRK1B	ENST00000348817.7	TSL:5	c.1700G>A	p.Arg567Gln	missense	Exon 12 of 12	ENSP00000221803.4	Q9Y463-3

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152034 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000257 AC: 58 AN: 225486 AF XY: 0.000322

Gnomad AFR exome AF: 0.0000746

Gnomad AMR exome AF: 0.0000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000638

Gnomad FIN exome AF: 0.00201

Gnomad NFE exome AF: 0.0000204

Gnomad OTH exome AF: 0.000543

GnomAD4 exome AF: 0.000102 AC: 148 AN: 1455306 Hom.: 0 Cov.: 33 AF XY: 0.000115 AC XY: 83 AN XY: 723702

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.0000229 AC: 1 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25890

East Asian (EAS) AF: 0.000659 AC: 26 AN: 39452

South Asian (SAS) AF: 0.00 AC: 0 AN: 85732

European-Finnish (FIN) AF: 0.00160 AC: 83 AN: 51880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1109542

Other (OTH) AF: 0.000117 AC: 7 AN: 60052

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152152 Hom.: 0 Cov.: 31 AF XY: 0.000336 AC XY: 25 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41508

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.000199 AC: 24

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DYRK1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.34	T
Polyphen		0.99	D
Vest4		0.30
MVP		0.64
MPC		1.4
ClinPred		0.079	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.35
Mutation Taster		=91/9	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: rs200681061; hg19: chr19-40316461;