19-39825836-G-A

Variant names:

• chr19-39825836-G-A
• NM_004714.3:c.1769C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004714.3(DYRK1B):​c.1769C>T​(p.Ser590Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,026 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 Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DYRK1B NM_004714.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.48
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32866842).

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.1769C>T	p.Ser590Leu	missense	Exon 11 of 11	NP_004705.1	Q9Y463-1
	DYRK1B	NM_006484.3		c.1685C>T	p.Ser562Leu	missense	Exon 12 of 12	NP_006475.1	Q9Y463-3
	DYRK1B	NM_006483.3		c.1649C>T	p.Ser550Leu	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.1769C>T	p.Ser590Leu	missense	Exon 11 of 11	ENSP00000312789.4	Q9Y463-1
	DYRK1B	ENST00000593685.5	TSL:5	c.1949C>T	p.Ser650Leu	missense	Exon 11 of 11	ENSP00000469863.2	A0A9H4CVU7
	DYRK1B	ENST00000348817.7	TSL:5	c.1685C>T	p.Ser562Leu	missense	Exon 12 of 12	ENSP00000221803.4	Q9Y463-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458026 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725178

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110660

Other (OTH) AF: 0.00 AC: 0 AN: 60202

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.20
BayesDel_addAF	Benign	-0.0065	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.074
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.076	T
Polyphen		0.81	P
Vest4		0.51
MutPred		0.30		Loss of glycosylation at S590 (P = 0.0099)
MVP		0.59
MPC		1.2
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.24
gMVP		0.37
Mutation Taster		=65/35	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

hg19: chr19-40316476;