Variant 1-206685327-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/21 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

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAPKAPK2	NM_032960.4 linkuse as main transcript	c.98C>G	p.Ala33Gly	missense_variant	1/10	ENST00000367103.4	NP_116584.2
MAPKAPK2	NM_004759.5 linkuse as main transcript	c.98C>G	p.Ala33Gly	missense_variant	1/10		NP_004750.1
MAPKAPK2	XM_005273353.4 linkuse as main transcript	c.98C>G	p.Ala33Gly	missense_variant	1/11		XP_005273410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK2	ENST00000367103.4 linkuse as main transcript	c.98C>G	p.Ala33Gly	missense_variant	1/10	1	NM_032960.4	ENSP00000356070	P1	P49137-1
MAPKAPK2	ENST00000294981.8 linkuse as main transcript	c.98C>G	p.Ala33Gly	missense_variant	1/10	1		ENSP00000294981		P49137-2

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

GnomAD3 exomes

AF:

0.000117

AC:

AN:

137288

Hom.:

AF XY:

0.0000906

AC XY:

AN XY:

77224

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 SAS exome

AF:

0.000199

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

Gnomad4 AFR exome

AF:

0.0000784

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000914

Gnomad4 SAS exome

AF:

0.000149

Gnomad4 FIN exome

AF:

0.0000669

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.0000746

AC:

AN:

147488

Hom.:

Cov.:

AF XY:

0.0000973

AC XY:

AN XY:

71968

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00119

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000604

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000453

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.000143

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.98C>G (p.A33G) alteration is located in exon 1 (coding exon 1) of the MAPKAPK2 gene. This alteration results from a C to G substitution at nucleotide position 98, causing the alanine (A) at amino acid position 33 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.079

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.39

T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.039

Sift

Benign

0.33

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.0020

B;B

Vest4

0.095

MutPred

0.18

Gain of catalytic residue at P29 (P = 0.1507);Gain of catalytic residue at P29 (P = 0.1507);

MVP

0.59

MPC

0.98

ClinPred

0.0074

GERP RS

1.6

Varity_R

0.075

gMVP

0.096

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over