rs782185154

Variant names:

• chr1-206728762-C-G
• rs782185154
• NM_032960.4:c.332C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-206728762-C-G
• chr1-206728762-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032960.4(MAPKAPK2):​c.332C>G​(p.Ala111Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A111V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKAPK2 NM_032960.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.332C>G	p.Ala111Gly	missense	Exon 2 of 10	NP_116584.2
	MAPKAPK2	NM_004759.5		c.332C>G	p.Ala111Gly	missense	Exon 2 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.332C>G	p.Ala111Gly	missense	Exon 2 of 10	ENSP00000356070.4	P49137-1
	MAPKAPK2	ENST00000294981.8	TSL:1	c.332C>G	p.Ala111Gly	missense	Exon 2 of 10	ENSP00000294981.4	P49137-2
	MAPKAPK2	ENST00000916346.1		c.332C>G	p.Ala111Gly	missense	Exon 2 of 10	ENSP00000586405.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000127 AC: 31 AN: 244478 AF XY: 0.0000903

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000883

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.000344

Gnomad NFE exome AF: 0.0000996

Gnomad OTH exome AF: 0.000167

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000130 AC: 19 AN: 1458200 Hom.: 0 Cov.: 32 AF XY: 0.0000152 AC XY: 11 AN XY: 725290

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000897 AC: 3 AN: 33432

American (AMR) AF: 0.0000680 AC: 3 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39394

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85978

European-Finnish (FIN) AF: 0.0000572 AC: 3 AN: 52474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5468

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111042

Other (OTH) AF: 0.00 AC: 0 AN: 60228

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.000404 AC: 49

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.26
Sift	Benign	0.059	T
Sift4G	Uncertain	0.057	T
Polyphen		0.98	D
Vest4		0.83
MutPred		0.66		Loss of stability (P = 0.0853)
MVP		0.71
MPC		1.1
ClinPred		0.070	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.73
Mutation Taster		=28/72	disease causing

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: rs782185154; hg19: chr1-206902107; COSMIC: COSV54314855; COSMIC: COSV54314855;