rs587777380

Positions:

• chr19-39830478-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_004714.3(DYRK1B):​c.269A>C​(p.His90Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYRK1B NM_004714.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.14

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-39830478-T-G is Pathogenic according to our data. Variant chr19-39830478-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 132793.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-39830478-T-G is described in UniProt as null. Variant chr19-39830478-T-G is described in UniProt as null.
• BP4: Computational evidence support a benign effect (MetaRNN=0.25671178). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK1B	NM_004714.3	c.269A>C	p.His90Pro	missense_variant	4/11	ENST00000323039.10	NP_004705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK1B	ENST00000323039.10	c.269A>C	p.His90Pro	missense_variant	4/11	1	NM_004714.3	ENSP00000312789	P1
	ENST00000706940.1			downstream_gene_variant				ENSP00000516660	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Abdominal obesity-metabolic syndrome 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 15, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.095	T;T;.;.;.;.;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.26	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;N;N;N;.;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	.;N;N;.;N;.;.
REVEL	Pathogenic	0.66
Sift	Benign	0.079	.;T;T;.;T;.;.
Sift4G	Uncertain	0.049	D;D;T;T;T;.;D
Polyphen		0.0	B;B;B;B;B;.;.
Vest4		0.85
MutPred		0.29		Loss of ubiquitination at K86 (P = 0.1296);Loss of ubiquitination at K86 (P = 0.1296);Loss of ubiquitination at K86 (P = 0.1296);Loss of ubiquitination at K86 (P = 0.1296);Loss of ubiquitination at K86 (P = 0.1296);Loss of ubiquitination at K86 (P = 0.1296);Loss of ubiquitination at K86 (P = 0.1296);
MVP		0.64
MPC		0.75
ClinPred		0.63	D
GERP RS		3.4
Varity_R		0.12
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs587777380; hg19: chr19-40321118;