19-39826691-G-C

Variant names:

• chr19-39826691-G-C
• rs773231614
• NM_004714.3:c.1392C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004714.3(DYRK1B):​c.1392C>G​(p.Ala464Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,604,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: DYRK1B NM_004714.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.89
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-39826691-G-C is Benign according to our data. Variant chr19-39826691-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 762925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK1B	NM_004714.3	c.1392C>G	p.Ala464Ala	synonymous_variant	Exon 9 of 11	ENST00000323039.10	NP_004705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK1B	ENST00000323039.10	c.1392C>G	p.Ala464Ala	synonymous_variant	Exon 9 of 11	1	NM_004714.3	ENSP00000312789.4

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152222 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 9 AN: 225954 AF XY: 0.0000728

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000503

Gnomad OTH exome AF: 0.000182

GnomAD4 exome AF: 0.0000262 AC: 38 AN: 1452084 Hom.: 0 Cov.: 32 AF XY: 0.0000374 AC XY: 27 AN XY: 721646

African (AFR) AF: 0.00 AC: 0 AN: 32946

American (AMR) AF: 0.00 AC: 0 AN: 43720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39082

South Asian (SAS) AF: 0.0000827 AC: 7 AN: 84598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51958

Middle Eastern (MID) AF: 0.000716 AC: 4 AN: 5586

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1108496

Other (OTH) AF: 0.0000667 AC: 4 AN: 59970

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152338 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74492

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000850 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 11, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DYRK1B-related disorder Benign:1

Feb 17, 2022

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	-0.56
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs773231614; hg19: chr19-40317331;