dbSNP rs45514798: MAPKAPK2:c.484+27G>A (chr1-206729126-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032960.4(MAPKAPK2):c.484+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,611,182 control chromosomes in the GnomAD database, including 28,886 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 0.13 ( 1647 hom., cov: 32)

Exomes 𝑓: 0.18 ( 27239 hom. )

Consequence

MAPKAPK2
NM_032960.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4 link	c.484+27G>A		intron_variant	Intron 3 of 9	ENST00000367103.4	NP_116584.2	P49137-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAPKAPK2	ENST00000367103.4 link	c.484+27G>A	intron_variant	Intron 3 of 9	1	NM_032960.4	ENSP00000356070.4	P49137-1
MAPKAPK2	ENST00000294981.8 link	c.484+27G>A	intron_variant	Intron 3 of 9	1		ENSP00000294981.4	P49137-2
MAPKAPK2	ENST00000493447.1 link	n.166+27G>A	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19210

AN:

152064

Hom.:

1647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0670

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.0909

GnomAD2 exomes

AF:

0.129

AC:

32225

AN:

249862

AF XY:

0.130

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.0923

Gnomad ASJ exome

AF:

0.0620

Gnomad EAS exome

AF:

0.00126

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.182

AC:

265920

AN:

1459000

Hom.:

27239

Cov.:

AF XY:

0.178

AC XY:

129339

AN XY:

725924

show subpopulations

African (AFR)

AF:

0.0277

AC:

927

AN:

33420

American (AMR)

AF:

0.0939

AC:

4182

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.0647

AC:

1691

AN:

26118

East Asian (EAS)

AF:

0.000655

AC:

AN:

39672

South Asian (SAS)

AF:

0.0718

AC:

6189

AN:

86186

European-Finnish (FIN)

AF:

0.179

AC:

9547

AN:

53366

Middle Eastern (MID)

AF:

0.0441

AC:

252

AN:

5714

European-Non Finnish (NFE)

AF:

0.211

AC:

233986

AN:

1109678

Other (OTH)

AF:

0.151

AC:

9120

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

11611

23222

34834

46445

58056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7996

15992

23988

31984

39980

<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:

0.126

AC:

19209

AN:

152182

Hom.:

1647

Cov.:

AF XY:

0.123

AC XY:

9179

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0344

AC:

1429

AN:

41544

American (AMR)

AF:

0.102

AC:

1565

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0616

AC:

214

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5174

South Asian (SAS)

AF:

0.0668

AC:

323

AN:

4832

European-Finnish (FIN)

AF:

0.177

AC:

1871

AN:

10572

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.197

AC:

13391

AN:

67980

Other (OTH)

AF:

0.0900

AC:

190

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

840

1680

2521

3361

4201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.148

Hom.:

364

Bravo

AF:

0.117

Asia WGS

AF:

0.0340

AC:

121

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.1

(source)

DANN

Benign

0.55

PhyloP100

0.65

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over