Variant rs16949924 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_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

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 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=-0.82).

BP6

Variant 15-66435259-G-C is Benign according to our data. Variant chr15-66435259-G-C is described in ClinVar as [Benign]. Clinvar id 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	MANE	Protein	UniProt
MAP2K1	NM_002755.4 link	c.291+22G>C	intron_variant	ENST00000307102.10	NP_002746.1	Q02750-1A4QPA9
MAP2K1	NM_001411065.1 link	c.225+22G>C	intron_variant		NP_001397994.1
MAP2K1	XM_011521783.4 link	c.225+22G>C	intron_variant		XP_011520085.1	B4DFY5
MAP2K1	XM_017022411.3 link	c.291+22G>C	intron_variant		XP_016877900.1	Q02750-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K1	ENST00000307102.10 link	c.291+22G>C		intron_variant		1	NM_002755.4	ENSP00000302486.5		Q02750-1

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

GnomAD3 exomes

AF:

0.319

AC:

80030

AN:

250750

Hom.:

13235

AF XY:

0.324

AC XY:

43972

AN XY:

135584

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 SAS exome

AF:

0.370

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

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.296

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.277

AC:

42130

AN:

151898

Hom.:

6512

Cov.:

AF XY:

0.278

AC XY:

20657

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.325

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.338

Gnomad4 OTH

AF:

0.289

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Squamous cell lung carcinoma

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing;in vivo

Faculté Pluridciplinaire Nador, Université Mohamed Premier

May 05, 2020

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cardiofaciocutaneous syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

DANN

Benign

0.70

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