Variant chr19-4090574-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030662.4(MAP2K2):c.*24C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,530,080 control chromosomes in the GnomAD database, including 25,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1993 hom., cov: 33)

Exomes 𝑓: 0.18 ( 23302 hom. )

Consequence

MAP2K2
NM_030662.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.854

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-4090574-G-A is Benign according to our data. Variant chr19-4090574-G-A is described in ClinVar as [Benign]. Clinvar id is 40848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
MAP2K2	NM_030662.4 linkuse as main transcript	c.*24C>T	3_prime_UTR_variant	11/11	ENST00000262948.10	NP_109587.1
MAP2K2	XM_006722799.3 linkuse as main transcript	c.*24C>T	3_prime_UTR_variant	9/9		XP_006722862.1
MAP2K2	XM_047439100.1 linkuse as main transcript	c.*24C>T	3_prime_UTR_variant	9/9		XP_047295056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K2	ENST00000262948.10 linkuse as main transcript	c.*24C>T		3_prime_UTR_variant	11/11	1	NM_030662.4	ENSP00000262948	P1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22270

AN:

152056

Hom.:

1994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.121

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.138

GnomAD3 exomes

AF:

0.182

AC:

27830

AN:

153264

Hom.:

2634

AF XY:

0.183

AC XY:

14844

AN XY:

81166

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.181

AC:

249161

AN:

1377906

Hom.:

23302

Cov.:

AF XY:

0.181

AC XY:

123236

AN XY:

680786

show subpopulations

Gnomad4 AFR exome

AF:

0.0311

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.146

AC:

22258

AN:

152174

Hom.:

1993

Cov.:

AF XY:

0.150

AC XY:

11189

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.110

Hom.:

238

Bravo

AF:

0.136

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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