19-39825706-G-C

Variant names:

• chr19-39825706-G-C
• rs370237703
• NM_004714.3:c.*9C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004714.3(DYRK1B):​c.*9C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,547,078 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: DYRK1B NM_004714.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 0.539
• 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), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS2: High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1B	NM_004714.3	c.*9C>G		3_prime_UTR_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.*9C>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_004714.3	ENSP00000312789.4

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 174 AN: 152044 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00102 AC: 147 AN: 144142 AF XY: 0.00107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.000606

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000320

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.000959

GnomAD4 exome AF: 0.00153 AC: 2136 AN: 1394916 Hom.: 4 Cov.: 33 AF XY: 0.00160 AC XY: 1098 AN XY: 688160

African (AFR) AF: 0.0000949 AC: 3 AN: 31600

American (AMR) AF: 0.000896 AC: 32 AN: 35726

Ashkenazi Jewish (ASJ) AF: 0.000596 AC: 15 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 35826

South Asian (SAS) AF: 0.000681 AC: 54 AN: 79302

European-Finnish (FIN) AF: 0.000351 AC: 16 AN: 45612

Middle Eastern (MID) AF: 0.000228 AC: 1 AN: 4378

European-Non Finnish (NFE) AF: 0.00181 AC: 1949 AN: 1079460

Other (OTH) AF: 0.00114 AC: 66 AN: 57852

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152162 Hom.: 1 Cov.: 31 AF XY: 0.00112 AC XY: 83 AN XY: 74398

African (AFR) AF: 0.000241 AC: 10 AN: 41522

American (AMR) AF: 0.00216 AC: 33 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4814

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00177 AC: 120 AN: 67984

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.00111

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 18, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DYRK1B-related disorder Benign:1

Jul 12, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		0.54
Mutation Taster		=100/0	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: rs370237703; hg19: chr19-40316346;