Genetic Variant MAPKAPK2:p.Pro32Ser (chr1-206685323-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032960.4(MAPKAPK2):c.94C>T(p.Pro32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. P32L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAPKAPK2
NM_032960.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.554

Publications

2 publications found

Variant links:

Genes affected

MAPKAPK2 (HGNC:6887): (MAPK activated protein kinase 2) This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MAPKAPK2 links:

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ACMG classification

Classification was made for transcript

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=0.0719839).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032960.4. 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
	MAPKAPK2	NM_032960.4	MANE Select	c.94C>T	p.Pro32Ser	missense	Exon 1 of 10	NP_116584.2
	MAPKAPK2	NM_004759.5		c.94C>T	p.Pro32Ser	missense	Exon 1 of 10	NP_004750.1	P49137-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPKAPK2	ENST00000367103.4	TSL:1 MANE Select	c.94C>T	p.Pro32Ser	missense	Exon 1 of 10	ENSP00000356070.4	P49137-1
MAPKAPK2	ENST00000294981.8	TSL:1	c.94C>T	p.Pro32Ser	missense	Exon 1 of 10	ENSP00000294981.4	P49137-2
MAPKAPK2	ENST00000916346.1		c.94C>T	p.Pro32Ser	missense	Exon 1 of 10	ENSP00000586405.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1271368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

630094

African (AFR)

AF:

0.00

AC:

AN:

25270

American (AMR)

AF:

0.00

AC:

AN:

27822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20376

East Asian (EAS)

AF:

0.00

AC:

AN:

24750

South Asian (SAS)

AF:

0.00

AC:

AN:

73076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1002318

Other (OTH)

AF:

0.00

AC:

AN:

49608

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

-0.55

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.41

REVEL

Benign

0.045

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.081

MutPred

0.27

Gain of phosphorylation at P32 (P = 0.0099)

MVP

0.54

MPC

0.98

ClinPred

0.058

GERP RS

2.6

PromoterAI

0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.038

gMVP

0.11

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over