rs557502236

Variant names:

• chr12-67649940-C-T
• rs557502236
• NM_006482.3:c.193C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-67649940-C-T
• chr12-67649940-C-G

Variant summary

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

The NM_006482.3(DYRK2):​c.193C>T​(p.His65Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,373,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: DYRK2 NM_006482.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88
• Publications: 0 publications found

Genes affected

DYRK2 (HGNC:3093): (dual specificity tyrosine phosphorylation regulated kinase 2) DYRK2 belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and/or development. The family is defined by structural similarity of their kinase domains and their capability to autophosphorylate on tyrosine residues. DYRK2 has demonstrated tyrosine autophosphorylation and catalyzed phosphorylation of histones H3 and H2B in vitro. Two isoforms of DYRK2 have been isolated. The predominant isoform, isoform 1, lacks a 5' terminal insert. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.021955192).
• BS2: High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006482.3. 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
	DYRK2	NM_006482.3	MANE Select	c.193C>T	p.His65Tyr	missense	Exon 2 of 3	NP_006473.2	Q92630-1
	DYRK2	NM_003583.4		c.-22+758C>T		intron	N/A	NP_003574.1	Q92630-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK2	ENST00000344096.4	TSL:1 MANE Select	c.193C>T	p.His65Tyr	missense	Exon 2 of 3	ENSP00000342105.4	Q92630-1
	DYRK2	ENST00000393555.3	TSL:1	c.-22+758C>T		intron	N/A	ENSP00000377186.3	Q92630-2
	DYRK2	ENST00000908892.1		c.193C>T	p.His65Tyr	missense	Exon 3 of 4	ENSP00000578951.1

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 30 AN: 151828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000242 AC: 9 AN: 37186 AF XY: 0.000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000821

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000169 AC: 207 AN: 1222010 Hom.: 0 Cov.: 30 AF XY: 0.000186 AC XY: 111 AN XY: 595666

African (AFR) AF: 0.00 AC: 0 AN: 24040

American (AMR) AF: 0.00 AC: 0 AN: 10506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19616

East Asian (EAS) AF: 0.00 AC: 0 AN: 27530

South Asian (SAS) AF: 0.00 AC: 0 AN: 50942

European-Finnish (FIN) AF: 0.000407 AC: 13 AN: 31952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3512

European-Non Finnish (NFE) AF: 0.000187 AC: 188 AN: 1003726

Other (OTH) AF: 0.000120 AC: 6 AN: 50186

GnomAD4 genome AF: 0.000197 AC: 30 AN: 151938 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74284

African (AFR) AF: 0.0000241 AC: 1 AN: 41484

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67888

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000215

ExAC AF: 0.0000894 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.042
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.085
Sift	Benign	0.56	T
Sift4G	Benign	1.0	T
Polyphen		0.022	B
Vest4		0.34
MutPred		0.38		Gain of catalytic residue at I67 (P = 0.0013)
MVP		0.57
MPC		0.65
ClinPred		0.095	T
GERP RS		3.5
PromoterAI		0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.36
Mutation Taster		=94/6	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: rs557502236; hg19: chr12-68043720;