ENST00000393555.3:c.-38C>T

Variant names:

• chr12-67649166-C-T
• rs200090077
• ENST00000393555.3:c.-38C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000393555.3(DYRK2):​c.-38C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000642 in 1,513,424 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: DYRK2 ENST00000393555.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07
• 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 (BayesDel_noAF=-0.34).
• BP6: Variant 12-67649166-C-T is Benign according to our data. Variant chr12-67649166-C-T is described in ClinVar as Benign. ClinVar VariationId is 790666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 536 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393555.3. 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.33C>T	p.Pro11Pro	synonymous	Exon 1 of 3	NP_006473.2	Q92630-1
	DYRK2	NM_003583.4		c.-38C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_003574.1	Q92630-2
	DYRK2	NM_003583.4		c.-38C>T		5_prime_UTR	Exon 1 of 2	NP_003574.1	Q92630-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYRK2	ENST00000393555.3	TSL:1	c.-38C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000377186.3	Q92630-2
	DYRK2	ENST00000344096.4	TSL:1 MANE Select	c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 3	ENSP00000342105.4	Q92630-1
	DYRK2	ENST00000393555.3	TSL:1	c.-38C>T		5_prime_UTR	Exon 1 of 2	ENSP00000377186.3	Q92630-2

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 536 AN: 151502 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000985

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.00337

GnomAD2 exomes AF: 0.000614 AC: 113 AN: 183950 AF XY: 0.000443

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000344

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000243

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000320 AC: 436 AN: 1361814 Hom.: 1 Cov.: 30 AF XY: 0.000244 AC XY: 165 AN XY: 677298

African (AFR) AF: 0.0123 AC: 343 AN: 27784

American (AMR) AF: 0.000588 AC: 21 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22908

East Asian (EAS) AF: 0.00 AC: 0 AN: 30208

South Asian (SAS) AF: 0.00 AC: 0 AN: 76972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49264

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5362

European-Non Finnish (NFE) AF: 0.0000340 AC: 36 AN: 1059050

Other (OTH) AF: 0.000641 AC: 35 AN: 54582

GnomAD4 genome AF: 0.00354 AC: 536 AN: 151610 Hom.: 6 Cov.: 31 AF XY: 0.00325 AC XY: 241 AN XY: 74100

African (AFR) AF: 0.0123 AC: 509 AN: 41488

American (AMR) AF: 0.000984 AC: 15 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10424

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

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67730

Other (OTH) AF: 0.00333 AC: 7 AN: 2102

Alfa AF: 0.0000590 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		-2.1
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Mutation Taster		=295/5	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: rs200090077; hg19: chr12-68042946;