rs16949924

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_002755.4(MAP2K1):c.291+22G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,596,254 control chromosomes in the GnomAD database, including 91,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6512 hom., cov: 31)

Exomes 𝑓: 0.34 ( 84717 hom. )

Consequence

MAP2K1
NM_002755.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 0.115

Publications

18 publications found

Variant links:

Genes affected

MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

MAP2K1 Gene-Disease associations (from GenCC):

cardiofaciocutaneous syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
cardiofaciocutaneous syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, ClinGen
Noonan syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MAP2K1 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=-0.82).

BP6

Variant 15-66435259-G-C is Benign according to our data. Variant chr15-66435259-G-C is described in ClinVar as Benign. ClinVar VariationId is 40784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MAP2K1	NM_002755.4 link	c.291+22G>C	intron_variant	Intron 2 of 10	ENST00000307102.10	NP_002746.1
MAP2K1	NM_001411065.1 link	c.225+22G>C	intron_variant	Intron 2 of 9		NP_001397994.1
MAP2K1	XM_011521783.4 link	c.225+22G>C	intron_variant	Intron 2 of 10		XP_011520085.1
MAP2K1	XM_017022411.3 link	c.291+22G>C	intron_variant	Intron 2 of 9		XP_016877900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K1	ENST00000307102.10 link	c.291+22G>C		intron_variant	Intron 2 of 10	1	NM_002755.4	ENSP00000302486.5

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42103

AN:

151780

Hom.:

6506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.319

AC:

80030

AN:

250750

AF XY:

0.324

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.338

AC:

488843

AN:

1444356

Hom.:

84717

Cov.:

AF XY:

0.339

AC XY:

243956

AN XY:

719736

show subpopulations

African (AFR)

AF:

0.136

AC:

4497

AN:

33128

American (AMR)

AF:

0.349

AC:

15590

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6183

AN:

25954

East Asian (EAS)

AF:

0.296

AC:

11717

AN:

39596

South Asian (SAS)

AF:

0.371

AC:

31848

AN:

85910

European-Finnish (FIN)

AF:

0.303

AC:

16151

AN:

53390

Middle Eastern (MID)

AF:

0.252

AC:

1449

AN:

5740

European-Non Finnish (NFE)

AF:

0.349

AC:

382422

AN:

1096140

Other (OTH)

AF:

0.318

AC:

18986

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

15621

31242

46862

62483

78104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12248

24496

36744

48992

61240

<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:

0.277

AC:

42130

AN:

151898

Hom.:

6512

Cov.:

AF XY:

0.278

AC XY:

20657

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.142

AC:

5902

AN:

41468

American (AMR)

AF:

0.325

AC:

4964

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

824

AN:

3418

East Asian (EAS)

AF:

0.314

AC:

1620

AN:

5162

South Asian (SAS)

AF:

0.368

AC:

1768

AN:

4808

European-Finnish (FIN)

AF:

0.297

AC:

3133

AN:

10532

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22985

AN:

67946

Other (OTH)

AF:

0.289

AC:

609

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1491

2982

4474

5965

7456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.285

Hom.:

1230

Bravo

AF:

0.272

Asia WGS

AF:

0.310

AC:

1080

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Squamous cell lung carcinoma

Uncertain:1

May 05, 2020

Faculté Pluridciplinaire Nador, Université Mohamed Premier

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing;in vivo

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiofaciocutaneous syndrome 3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.82

CADD

Benign

5.5

(source)

DANN

Benign

0.70

PhyloP100

0.12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over