Variant rs350916 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.1047-279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 515,488 control chromosomes in the GnomAD database, including 60,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15847 hom., cov: 33)

Exomes 𝑓: 0.49 ( 44388 hom. )

Consequence

MAP2K2
NM_030662.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.388

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 -20 ACMG points.

BP4

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

BP6

Variant 19-4094777-G-A is Benign according to our data. Variant chr19-4094777-G-A is described in ClinVar as [Benign]. Clinvar id is 561820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAP2K2	NM_030662.4 link	c.1047-279C>T	intron_variant	ENST00000262948.10	NP_109587.1	P36507
MAP2K2	XM_006722799.3 link	c.768-279C>T	intron_variant		XP_006722862.1
MAP2K2	XM_047439100.1 link	c.477-279C>T	intron_variant		XP_047295056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K2	ENST00000262948.10 link	c.1047-279C>T		intron_variant		1	NM_030662.4	ENSP00000262948.4		P36507

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67881

AN:

151962

Hom.:

15839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.487

AC:

177030

AN:

363410

Hom.:

44388

Cov.:

AF XY:

0.483

AC XY:

91217

AN XY:

189012

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.557

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.620

Gnomad4 SAS exome

AF:

0.410

Gnomad4 FIN exome

AF:

0.487

Gnomad4 NFE exome

AF:

0.489

Gnomad4 OTH exome

AF:

0.482

GnomAD4 genome

AF:

0.447

AC:

67913

AN:

152078

Hom.:

15847

Cov.:

AF XY:

0.447

AC XY:

33207

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.545

Gnomad4 ASJ

AF:

0.498

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.490

Gnomad4 OTH

AF:

0.470

Alfa

AF:

0.480

Hom.:

20326

Bravo

AF:

0.447

Asia WGS

AF:

0.493

AC:

1716

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jun 18, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.0

DANN

Benign

0.76

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