rs350916

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

cardiofaciocutaneous syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
cardiofaciocutaneous syndrome 4
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Noonan syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome-like disorder with loose anagen hair
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MAP2K2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030662.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP2K2	NM_030662.4	MANE Select	c.1047-279C>T	intron	N/A	NP_109587.1	P36507
MAP2K2	NM_001440688.1		c.768-279C>T	intron	N/A	NP_001427617.1
MAP2K2	NM_001440689.1		c.477-279C>T	intron	N/A	NP_001427618.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP2K2	ENST00000262948.10	TSL:1 MANE Select	c.1047-279C>T	intron	N/A	ENSP00000262948.4	P36507
MAP2K2	ENST00000945862.1		c.1047-90C>T	intron	N/A	ENSP00000615921.1
MAP2K2	ENST00000897166.1		c.1047-120C>T	intron	N/A	ENSP00000567225.1

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

African (AFR)

AF:

0.293

AC:

3261

AN:

11142

American (AMR)

AF:

0.557

AC:

8711

AN:

15640

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

6026

AN:

11724

East Asian (EAS)

AF:

0.620

AC:

16149

AN:

26048

South Asian (SAS)

AF:

0.410

AC:

15530

AN:

37894

European-Finnish (FIN)

AF:

0.487

AC:

10862

AN:

22290

Middle Eastern (MID)

AF:

0.461

AC:

729

AN:

1582

European-Non Finnish (NFE)

AF:

0.489

AC:

105381

AN:

215554

Other (OTH)

AF:

0.482

AC:

10381

AN:

21536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4362

8724

13087

17449

21811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.447

AC:

67913

AN:

152078

Hom.:

15847

Cov.:

AF XY:

0.447

AC XY:

33207

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.303

AC:

12570

AN:

41522

American (AMR)

AF:

0.545

AC:

8337

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1726

AN:

3468

East Asian (EAS)

AF:

0.652

AC:

3345

AN:

5128

South Asian (SAS)

AF:

0.407

AC:

1962

AN:

4824

European-Finnish (FIN)

AF:

0.479

AC:

5079

AN:

10598

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33285

AN:

67934

Other (OTH)

AF:

0.470

AC:

991

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1948

3896

5845

7793

9741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.479

Hom.:

25741

Bravo

AF:

0.447

Asia WGS

AF:

0.493

AC:

1716

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.0

(source)

DANN

Benign

0.76

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over