chr19-39825910-A-T

Position:

• chr19-39825910-A-T

Variant summary

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

The NM_004714.3(DYRK1B):​c.1695T>A​(p.Asp565Glu) 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. 14/21 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: 0.194

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=0.09433833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYRK1B	NM_004714.3	c.1695T>A	p.Asp565Glu	missense_variant	11/11	ENST00000323039.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYRK1B	ENST00000323039.10	c.1695T>A	p.Asp565Glu	missense_variant	11/11	1	NM_004714.3	P1

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

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 11, 2023

This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 565 of the DYRK1B protein (p.Asp565Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYRK1B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DYRK1B protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T;T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.58	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.094	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N;N;.;.;.
MutationTaster	Benign	0.96	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.51	.;N;N;.;N
REVEL	Benign	0.032
Sift	Benign	0.43	.;T;T;.;T
Sift4G	Benign	0.62	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.14
MutPred		0.38		Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);.;.;.;
MVP		0.48
MPC		1.3
ClinPred		0.16	T
GERP RS		2.6
Varity_R		0.026
gMVP		0.088

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: chr19-40316550;