rs8157

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.192C>T (p.Val64=) variant in the MAP2K2 gene is 7.417% (1283/16512) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) LINK:https://erepo.genome.network/evrepo/ui/classification/CA137916/MONDO:0021060/004

Frequency

Genomes: 𝑓 0.064 ( 326 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3047 hom. )

Consequence

MAP2K2
NM_030662.4 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:8

Conservation

PhyloP100: -2.81

Variant links:

Genes affected

MAP2K2 (HGNC:6842): (mitogen-activated protein kinase kinase 2) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]

MAP2K2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K2	NM_030662.4 link	c.192C>T	p.Val64Val	synonymous_variant	Exon 2 of 11	ENST00000262948.10	NP_109587.1	P36507
MAP2K2	XM_006722799.3 link	c.192C>T	p.Val64Val	synonymous_variant	Exon 2 of 9		XP_006722862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAP2K2	ENST00000262948.10 link	c.192C>T	p.Val64Val	synonymous_variant	Exon 2 of 11	1	NM_030662.4	ENSP00000262948.4	P36507
MAP2K2	ENST00000394867.9 link	n.631C>T		non_coding_transcript_exon_variant	Exon 1 of 10	5
MAP2K2	ENST00000599345.1 link	n.389C>T		non_coding_transcript_exon_variant	Exon 2 of 7	5
MAP2K2	ENST00000687128.1 link	n.631C>T		non_coding_transcript_exon_variant	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.0639

AC:

9714

AN:

152126

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0192

Gnomad SAS

AF:

0.0693

Gnomad FIN

AF:

0.0711

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0595

AC:

14949

AN:

251330

Hom.:

527

AF XY:

0.0619

AC XY:

8417

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0761

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.0560

Gnomad EAS exome

AF:

0.0242

Gnomad SAS exome

AF:

0.0784

Gnomad FIN exome

AF:

0.0769

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0613

GnomAD4 exome

AF:

0.0624

AC:

91175

AN:

1461766

Hom.:

3047

Cov.:

AF XY:

0.0630

AC XY:

45842

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0760

Gnomad4 AMR exome

AF:

0.0304

Gnomad4 ASJ exome

AF:

0.0537

Gnomad4 EAS exome

AF:

0.0142

Gnomad4 SAS exome

AF:

0.0781

Gnomad4 FIN exome

AF:

0.0784

Gnomad4 NFE exome

AF:

0.0634

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

AF:

0.0638

AC:

9718

AN:

152244

Hom.:

326

Cov.:

AF XY:

0.0627

AC XY:

4664

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0768

Gnomad4 AMR

AF:

0.0405

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.0193

Gnomad4 SAS

AF:

0.0697

Gnomad4 FIN

AF:

0.0711

Gnomad4 NFE

AF:

0.0646

Gnomad4 OTH

AF:

0.0595

Alfa

AF:

0.0634

Hom.:

128

Bravo

AF:

0.0614

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.0667

EpiControl

AF:

0.0587

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 18, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 11, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RASopathy

Benign:2

May 09, 2017

ClinGen RASopathy Variant Curation Expert Panel

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The filtering allele frequency of the c.192C>T (p.Val64=) variant in the MAP2K2 gene is 7.417% (1283/16512) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cardiovascular phenotype

Benign:1

Apr 17, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Cardiofaciocutaneous syndrome 4

Benign:1

Nov 20, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.2

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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