rs12602109

Positions:

• chr17-21313290-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3	c.915-202G>A		intron_variant		ENST00000342679.9	NP_659731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9	c.915-202G>A		intron_variant		1	NM_145109.3	ENSP00000345083	P1

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

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.269

Alfa AF: 0.243 Hom.: 1302

Bravo AF: 0.288

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

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