rs1442897061

Variant names:

• chr19-39825806-C-G
• rs1442897061
• NM_004714.3:c.1799G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-39825806-C-G
• chr19-39825806-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004714.3(DYRK1B):​c.1799G>C​(p.Arg600Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,696 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R600H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DYRK1B NM_004714.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21548134).

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.1799G>C	p.Arg600Pro	missense	Exon 11 of 11	NP_004705.1	Q9Y463-1
	DYRK1B	NM_006484.3		c.1715G>C	p.Arg572Pro	missense	Exon 12 of 12	NP_006475.1	Q9Y463-3
	DYRK1B	NM_006483.3		c.1679G>C	p.Arg560Pro	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.1799G>C	p.Arg600Pro	missense	Exon 11 of 11	ENSP00000312789.4	Q9Y463-1
	DYRK1B	ENST00000593685.5	TSL:5	c.1979G>C	p.Arg660Pro	missense	Exon 11 of 11	ENSP00000469863.2	A0A9H4CVU7
	DYRK1B	ENST00000348817.7	TSL:5	c.1715G>C	p.Arg572Pro	missense	Exon 12 of 12	ENSP00000221803.4	Q9Y463-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439696 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 714746

African (AFR) AF: 0.00 AC: 0 AN: 33030

American (AMR) AF: 0.00 AC: 0 AN: 40546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25674

East Asian (EAS) AF: 0.00 AC: 0 AN: 38314

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5454

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102348

Other (OTH) AF: 0.00 AC: 0 AN: 59502

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.4
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.11
Sift	Uncertain	0.023	D
Sift4G	Benign	0.26	T
Polyphen		0.75	P
Vest4		0.37
MutPred		0.29		Loss of methylation at R600 (P = 0.0087)
MVP		0.62
MPC		1.7
ClinPred		0.88	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.19
Mutation Taster		=77/23	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: rs1442897061; hg19: chr19-40316446;