rs1555782801

Variant names:

• chr19-39825964-T-G
• rs1555782801
• NM_004714.3:c.1641A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004714.3(DYRK1B):​c.1641A>C​(p.Arg547Arg) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DYRK1B NM_004714.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.420
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-39825964-T-G is Benign according to our data. Variant chr19-39825964-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 435016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.42 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	NM_004714.3	MANE Select	c.1641A>C	p.Arg547Arg	synonymous	Exon 11 of 11	NP_004705.1
	DYRK1B	NM_006484.3		c.1557A>C	p.Arg519Arg	synonymous	Exon 12 of 12	NP_006475.1
	DYRK1B	NM_006483.3		c.1521A>C	p.Arg507Arg	synonymous	Exon 11 of 11	NP_006474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	ENST00000323039.10	TSL:1 MANE Select	c.1641A>C	p.Arg547Arg	synonymous	Exon 11 of 11	ENSP00000312789.4
	DYRK1B	ENST00000593685.5	TSL:5	c.1821A>C	p.Arg607Arg	synonymous	Exon 11 of 11	ENSP00000469863.2
	DYRK1B	ENST00000348817.7	TSL:5	c.1557A>C	p.Arg519Arg	synonymous	Exon 12 of 12	ENSP00000221803.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1365300 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 670472

African (AFR) AF: 0.00 AC: 0 AN: 30362

American (AMR) AF: 0.00 AC: 0 AN: 30802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19846

East Asian (EAS) AF: 0.00 AC: 0 AN: 38542

South Asian (SAS) AF: 0.00 AC: 0 AN: 71496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066356

Other (OTH) AF: 0.00 AC: 0 AN: 55972

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		-0.42
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: rs1555782801; hg19: chr19-40316604;