Variant 2-127307740-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371910.2(MAP3K2):c.1699A>G(p.Met567Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

MAP3K2
NM_001371910.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

MAP3K2 (HGNC:6854): (mitogen-activated protein kinase kinase kinase 2) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate Ikappa B kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process. [provided by RefSeq, Jul 2008]

MAP3K2 links:

ENSG00000286145 (HGNC:):

ENSG00000286145 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K2	NM_001371910.2 linkuse as main transcript	c.1699A>G	p.Met567Val	missense_variant	17/17	ENST00000682094.1	NP_001358839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K2	ENST00000682094.1 linkuse as main transcript	c.1699A>G	p.Met567Val	missense_variant	17/17		NM_001371910.2	ENSP00000507315.1		Q9Y2U5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000446

AC:

AN:

224170

Hom.:

AF XY:

0.00000827

AC XY:

AN XY:

120960

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAP3K2-related condition

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 27, 2024

The MAP3K2 c.1699A>G variant is predicted to result in the amino acid substitution p.Met567Val. This variant was reported in an individual with autism (Data S3 as 2:128065316:T:C, Zhou et al. 2022. PubMed ID: 35982159). This variant is reported in 0.0010% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.35

Sift

Benign

0.27

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.39

B;B

Vest4

0.62

MutPred

0.60

Loss of ubiquitination at K572 (P = 0.0997);Loss of ubiquitination at K572 (P = 0.0997);

MVP

0.80

MPC

1.0

ClinPred

0.94

GERP RS

5.7

Varity_R

0.39

gMVP

0.94

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