12-67649923-A-G

Variant names:

• chr12-67649923-A-G
• rs753955862
• NM_006482.3:c.176A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006482.3(DYRK2):​c.176A>G​(p.Asn59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000651 in 1,228,190 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: DYRK2 NM_006482.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08027062).
• BS2: High AC in GnomAdExome4 at 8 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.176A>G	p.Asn59Ser	missense	Exon 2 of 3	NP_006473.2	Q92630-1
	DYRK2	NM_003583.4		c.-22+741A>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.176A>G	p.Asn59Ser	missense	Exon 2 of 3	ENSP00000342105.4	Q92630-1
	DYRK2	ENST00000393555.3	TSL:1	c.-22+741A>G		intron	N/A	ENSP00000377186.3	Q92630-2
	DYRK2	ENST00000908892.1		c.176A>G	p.Asn59Ser	missense	Exon 3 of 4	ENSP00000578951.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000210 AC: 1 AN: 47714 AF XY: 0.0000348

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000651 AC: 8 AN: 1228190 Hom.: 0 Cov.: 30 AF XY: 0.0000100 AC XY: 6 AN XY: 599088

African (AFR) AF: 0.0000822 AC: 2 AN: 24338

American (AMR) AF: 0.00 AC: 0 AN: 12026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19516

East Asian (EAS) AF: 0.0000356 AC: 1 AN: 28116

South Asian (SAS) AF: 0.0000197 AC: 1 AN: 50858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3538

European-Non Finnish (NFE) AF: 0.00000199 AC: 2 AN: 1006588

Other (OTH) AF: 0.0000397 AC: 2 AN: 50386

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000954 AC: 1

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	0.055
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.098
Sift	Benign	0.23	T
Sift4G	Benign	0.85	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.28		Gain of catalytic residue at L55 (P = 0)
MVP		0.64
MPC		0.41
ClinPred		0.25	T
GERP RS		3.2
PromoterAI		-0.028	Neutral
Varity_R		0.051
gMVP		0.31
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753955862; hg19: chr12-68043703;