NM_004714.3:c.1860T>C

Variant names:

• chr19-39825745-A-G
• rs1968495871
• NM_004714.3:c.1860T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004714.3(DYRK1B):​c.1860T>C​(p.Gly620Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,406,450 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 (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: DYRK1B NM_004714.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.12
• 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), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 19-39825745-A-G is Benign according to our data. Variant chr19-39825745-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3349754.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	NM_004714.3	MANE Select	c.1860T>C	p.Gly620Gly	synonymous	Exon 11 of 11	NP_004705.1	Q9Y463-1
	DYRK1B	NM_006484.3		c.1776T>C	p.Gly592Gly	synonymous	Exon 12 of 12	NP_006475.1	Q9Y463-3
	DYRK1B	NM_006483.3		c.1740T>C	p.Gly580Gly	synonymous	Exon 11 of 11	NP_006474.1	Q9Y463-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK1B	ENST00000323039.10	TSL:1 MANE Select	c.1860T>C	p.Gly620Gly	synonymous	Exon 11 of 11	ENSP00000312789.4	Q9Y463-1
	DYRK1B	ENST00000593685.5	TSL:5	c.2040T>C	p.Gly680Gly	synonymous	Exon 11 of 11	ENSP00000469863.2	A0A9H4CVU7
	DYRK1B	ENST00000348817.7	TSL:5	c.1776T>C	p.Gly592Gly	synonymous	Exon 12 of 12	ENSP00000221803.4	Q9Y463-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000498 AC: 7 AN: 1406450 Hom.: 0 Cov.: 33 AF XY: 0.00000432 AC XY: 3 AN XY: 694618

African (AFR) AF: 0.00 AC: 0 AN: 31944

American (AMR) AF: 0.00 AC: 0 AN: 36210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25276

East Asian (EAS) AF: 0.00 AC: 0 AN: 36250

South Asian (SAS) AF: 0.00 AC: 0 AN: 80382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4898

European-Non Finnish (NFE) AF: 0.00000646 AC: 7 AN: 1084294

Other (OTH) AF: 0.00 AC: 0 AN: 58298

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DYRK1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.2
DANN	Benign	0.71
PhyloP100		2.1

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: rs1968495871; hg19: chr19-40316385;