12-67649940-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006482.3(DYRK2):​c.193C>G​(p.His65Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000164 in 1,222,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H65Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: DYRK2 NM_006482.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24033585).

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>G	p.His65Asp	missense	Exon 2 of 3	NP_006473.2	Q92630-1
	DYRK2	NM_003583.4		c.-22+758C>G		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>G	p.His65Asp	missense	Exon 2 of 3	ENSP00000342105.4	Q92630-1
	DYRK2	ENST00000393555.3	TSL:1	c.-22+758C>G		intron	N/A	ENSP00000377186.3	Q92630-2
	DYRK2	ENST00000908892.1		c.193C>G	p.His65Asp	missense	Exon 3 of 4	ENSP00000578951.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1222010 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 595666

African (AFR) AF: 0.0000416 AC: 1 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: 0.00 AC: 0 AN: 31952

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1003726

Other (OTH) AF: 0.0000199 AC: 1 AN: 50186

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.00051	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.21	T
Polyphen		0.40	B
Vest4		0.34
MutPred		0.33		Gain of catalytic residue at I67 (P = 8e-04)
MVP		0.65
MPC		0.73
ClinPred		0.75	D
GERP RS		3.5
PromoterAI		0.088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.43
Mutation Taster		=85/15	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;