chr19-39825791-G-C

Variant names:

• chr19-39825791-G-C
• NM_004714.3:c.1814C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004714.3(DYRK1B):​c.1814C>G​(p.Pro605Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DYRK1B NM_004714.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2250798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1B	NM_004714.3	c.1814C>G	p.Pro605Arg	missense_variant	Exon 11 of 11	ENST00000323039.10	NP_004705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1B	ENST00000323039.10	c.1814C>G	p.Pro605Arg	missense_variant	Exon 11 of 11	1	NM_004714.3	ENSP00000312789.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

DYRK1B-related disorder Uncertain:1

Apr 24, 2023

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The DYRK1B c.1814C>G variant is predicted to result in the amino acid substitution p.Pro605Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;T;.;.;.
Eigen	Benign	-0.022
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N;N;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.030	.;N;N;.;N
REVEL	Benign	0.089
Sift	Benign	0.045	.;D;D;.;T
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		0.84	P;P;P;P;P
Vest4		0.32
MutPred		0.30		Loss of glycosylation at P605 (P = 0.0079);Loss of glycosylation at P605 (P = 0.0079);.;.;.;
MVP		0.54
MPC		1.4
ClinPred		0.44	T
GERP RS		3.9
Varity_R		0.10
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-40316431;