rs12602109

Variant names:

• chr17-21313290-G-A
• rs12602109
• NM_145109.3:c.915-202G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145109.3(MAP2K3):​c.915-202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,054 control chromosomes in the GnomAD database, including 6,833 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6833 hom., cov: 32)
• Consequence: MAP2K3 NM_145109.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 4 publications found

Genes affected

MAP2K3 (HGNC:6843): (mitogen-activated protein kinase kinase 3) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145109.3. 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
	MAP2K3	NM_145109.3	MANE Select	c.915-202G>A		intron	N/A	NP_659731.1	P46734-1
	MAP2K3	NM_001316332.2		c.828-202G>A		intron	N/A	NP_001303261.1	P46734-2
	MAP2K3	NM_002756.4		c.828-202G>A		intron	N/A	NP_002747.2	P46734-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K3	ENST00000342679.9	TSL:1 MANE Select	c.915-202G>A		intron	N/A	ENSP00000345083.4	P46734-1
	MAP2K3	ENST00000910861.1		c.915-202G>A		intron	N/A	ENSP00000580920.1
	MAP2K3	ENST00000910862.1		c.915-202G>A		intron	N/A	ENSP00000580921.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43932 AN: 151936 Hom.: 6818 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43969 AN: 152054 Hom.: 6833 Cov.: 32 AF XY: 0.290 AC XY: 21521 AN XY: 74324

African (AFR) AF: 0.399 AC: 16543 AN: 41454

American (AMR) AF: 0.201 AC: 3068 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1689 AN: 5148

South Asian (SAS) AF: 0.340 AC: 1638 AN: 4824

European-Finnish (FIN) AF: 0.257 AC: 2719 AN: 10586

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16535 AN: 67966

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.243 Hom.: 1522

Bravo AF: 0.288

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.49
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs12602109; hg19: chr17-21216602; COSMIC: COSV57567630;