chr19-4090424-G-T

Position:

• chr19-4090424-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030662.4(MAP2K2):​c.*174C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 656,426 control chromosomes in the GnomAD database, including 7,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3989 hom., cov: 33)
  • Exomes 𝑓: 0.098 (3498 hom.)
• Consequence: MAP2K2 NM_030662.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-4090424-G-T is Benign according to our data. Variant chr19-4090424-G-T is described in ClinVar as [Benign]. Clinvar id is 1220587.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K2	NM_030662.4	c.*174C>A		3_prime_UTR_variant	11/11	ENST00000262948.10
MAP2K2	XM_006722799.3	c.*174C>A		3_prime_UTR_variant	9/9
MAP2K2	XM_047439100.1	c.*174C>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K2	ENST00000262948.10	c.*174C>A		3_prime_UTR_variant	11/11	1	NM_030662.4	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27007 AN: 152126 Hom.: 3988 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.0978 AC: 49311 AN: 504182 Hom.: 3498 Cov.: 5 AF XY: 0.0963 AC XY: 25739 AN XY: 267352

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.0829

Gnomad4 EAS exome AF: 0.000190

Gnomad4 SAS exome AF: 0.0919

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.0944

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.178 AC: 27029 AN: 152244 Hom.: 3989 Cov.: 33 AF XY: 0.174 AC XY: 12921 AN XY: 74440

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0789

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0528 Hom.: 50

Bravo AF: 0.187

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.71
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

Other links and lift over

dbSNP: rs6630; hg19: chr19-4090422;