15-66387311-TC-TCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002755.4(MAP2K1):c.-31dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,516,248 control chromosomes in the GnomAD database, including 8,983 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 977 hom., cov: 31)

Exomes 𝑓: 0.095 ( 8006 hom. )

Consequence

MAP2K1
NM_002755.4 5_prime_UTR

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.965

Publications

5 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 -16 ACMG points.

BP6

Variant 15-66387311-T-TC is Benign according to our data. Variant chr15-66387311-T-TC is described in ClinVar as [Benign]. Clinvar id is 40710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K1	NM_002755.4 link	c.-31dupC		5_prime_UTR_variant	Exon 1 of 11	ENST00000307102.10	NP_002746.1	Q02750-1A4QPA9
MAP2K1	XM_017022411.3 link	c.-31dupC		5_prime_UTR_variant	Exon 1 of 10		XP_016877900.1	Q02750-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K1	ENST00000307102.10 link	c.-31dupC		5_prime_UTR_variant	Exon 1 of 11	1	NM_002755.4	ENSP00000302486.5		Q02750-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15489

AN:

151718

Hom.:

978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0940

Gnomad AMI

AF:

0.0463

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0818

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.119

AC:

18384

AN:

154242

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.0905

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.0807

Gnomad NFE exome

AF:

0.0832

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.0947

AC:

129233

AN:

1364416

Hom.:

8006

Cov.:

AF XY:

0.0947

AC XY:

63904

AN XY:

675044

show subpopulations

African (AFR)

AF:

0.0910

AC:

2813

AN:

30898

American (AMR)

AF:

0.156

AC:

5573

AN:

35664

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3216

AN:

24886

East Asian (EAS)

AF:

0.369

AC:

13097

AN:

35512

South Asian (SAS)

AF:

0.0964

AC:

7575

AN:

78562

European-Finnish (FIN)

AF:

0.0832

AC:

4073

AN:

48968

Middle Eastern (MID)

AF:

0.0991

AC:

544

AN:

5490

European-Non Finnish (NFE)

AF:

0.0824

AC:

86282

AN:

1047686

Other (OTH)

AF:

0.107

AC:

6060

AN:

56750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

5651

11301

16952

22602

28253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.102

AC:

15484

AN:

151832

Hom.:

977

Cov.:

AF XY:

0.103

AC XY:

7636

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.0938

AC:

3887

AN:

41440

American (AMR)

AF:

0.133

AC:

2026

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1721

AN:

5102

South Asian (SAS)

AF:

0.111

AC:

533

AN:

4810

European-Finnish (FIN)

AF:

0.0818

AC:

862

AN:

10542

Middle Eastern (MID)

AF:

0.110

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0836

AC:

5679

AN:

67898

Other (OTH)

AF:

0.115

AC:

243

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

698

1396

2093

2791

3489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0935

Hom.:

136

Bravo

AF:

0.108

Asia WGS

AF:

0.205

AC:

709

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 07, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 15, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.96

Mutation Taster

=300/0

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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15-66387311-TC-TCC

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