chr1-206685323-C-G

Variant names:

• chr1-206685323-C-G
• rs782064315
• NM_032960.4:c.94C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032960.4(MAPKAPK2):​c.94C>G​(p.Pro32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,419,704 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 (★). 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: 𝑓 0.00010 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MAPKAPK2 NM_032960.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.554
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.05351931).
• BS2: High AC in GnomAd4 at 15 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.94C>G	p.Pro32Ala	missense	Exon 1 of 10	NP_116584.2
	MAPKAPK2	NM_004759.5		c.94C>G	p.Pro32Ala	missense	Exon 1 of 10	NP_004750.1	P49137-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAPK2	ENST00000367103.4	TSL:1 MANE Select	c.94C>G	p.Pro32Ala	missense	Exon 1 of 10	ENSP00000356070.4	P49137-1
	MAPKAPK2	ENST00000294981.8	TSL:1	c.94C>G	p.Pro32Ala	missense	Exon 1 of 10	ENSP00000294981.4	P49137-2
	MAPKAPK2	ENST00000916346.1		c.94C>G	p.Pro32Ala	missense	Exon 1 of 10	ENSP00000586405.1

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 148336 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000195

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000237 AC: 3 AN: 126600 AF XY: 0.0000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000578

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 172 AN: 1271368 Hom.: 0 Cov.: 23 AF XY: 0.000117 AC XY: 74 AN XY: 630094

African (AFR) AF: 0.0000791 AC: 2 AN: 25270

American (AMR) AF: 0.00 AC: 0 AN: 27822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20376

East Asian (EAS) AF: 0.00 AC: 0 AN: 24750

South Asian (SAS) AF: 0.00 AC: 0 AN: 73076

European-Finnish (FIN) AF: 0.0000896 AC: 4 AN: 44644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3504

European-Non Finnish (NFE) AF: 0.000158 AC: 158 AN: 1002318

Other (OTH) AF: 0.000161 AC: 8 AN: 49608

GnomAD4 genome AF: 0.000101 AC: 15 AN: 148336 Hom.: 0 Cov.: 30 AF XY: 0.0000968 AC XY: 7 AN XY: 72322

African (AFR) AF: 0.0000245 AC: 1 AN: 40886

American (AMR) AF: 0.00 AC: 0 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4776

European-Finnish (FIN) AF: 0.000107 AC: 1 AN: 9346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000195 AC: 13 AN: 66580

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.000199 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000256 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.55
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.36	N
REVEL	Benign	0.049
Sift	Benign	0.59	T
Sift4G	Benign	0.24	T
Polyphen		0.0050	B
Vest4		0.11
MutPred		0.28		Loss of glycosylation at P32 (P = 0.0016)
MVP		0.58
MPC		0.94
ClinPred		0.028	T
GERP RS		2.6
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.026
gMVP		0.087
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs782064315; hg19: chr1-206858668; COSMIC: COSV99685780; COSMIC: COSV99685780;