Genetic Variant MAPKAPK2:p.Ala33Gly (chr1-206685327-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032960.4(MAPKAPK2):c.98C>G(p.Ala33Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 1,427,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000075 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

MAPKAPK2
NM_032960.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.906

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007981956).

BS2

High AC in GnomAd4 at 11 AD gene.

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.98C>G	p.Ala33Gly	missense	Exon 1 of 10	NP_116584.2
	MAPKAPK2	NM_004759.5		c.98C>G	p.Ala33Gly	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.98C>G	p.Ala33Gly	missense	Exon 1 of 10	ENSP00000356070.4	P49137-1
MAPKAPK2	ENST00000294981.8	TSL:1	c.98C>G	p.Ala33Gly	missense	Exon 1 of 10	ENSP00000294981.4	P49137-2
MAPKAPK2	ENST00000916346.1		c.98C>G	p.Ala33Gly	missense	Exon 1 of 10	ENSP00000586405.1

Frequencies

GnomAD3 genomes

AF:

0.0000746

AC:

AN:

147380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00119

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000604

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000117

AC:

AN:

137288

AF XY:

0.0000906

show subpopulations

Gnomad AFR exome

AF:

0.000231

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000881

Gnomad FIN exome

AF:

0.0000591

Gnomad NFE exome

AF:

0.0000688

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000594

AC:

AN:

1279592

Hom.:

Cov.:

AF XY:

0.0000630

AC XY:

AN XY:

634776

show subpopulations

African (AFR)

AF:

0.0000784

AC:

AN:

25522

American (AMR)

AF:

0.00

AC:

AN:

28940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20358

East Asian (EAS)

AF:

0.000914

AC:

AN:

25168

South Asian (SAS)

AF:

0.000149

AC:

AN:

73622

European-Finnish (FIN)

AF:

0.0000669

AC:

AN:

44826

Middle Eastern (MID)

AF:

0.000286

AC:

AN:

3496

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

1007820

Other (OTH)

AF:

0.000120

AC:

AN:

49840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000746

AC:

AN:

147488

Hom.:

Cov.:

AF XY:

0.0000973

AC XY:

AN XY:

71968

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40738

American (AMR)

AF:

0.00

AC:

AN:

14944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.00119

AC:

AN:

5044

South Asian (SAS)

AF:

0.00

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000604

AC:

AN:

66178

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000453

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.000143

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.079

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.91

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.060

REVEL

Benign

0.039

Sift

Benign

0.33

Sift4G

Benign

0.46

Polyphen

0.0020

Vest4

0.095

MutPred

0.18

Gain of catalytic residue at P29 (P = 0.1507)

MVP

0.59

MPC

0.98

ClinPred

0.0074

GERP RS

1.6

PromoterAI

-0.096

Neutral

(source)

Varity_R

0.075

gMVP

0.096

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over