Variant 17-69526648-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002758.4(MAP2K6):c.820C>T(p.Pro274Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MAP2K6
NM_002758.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

MAP2K6 (HGNC:6846): (mitogen-activated protein kinase kinase 6) This gene encodes a member of the dual specificity protein kinase family, which functions 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 phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis. [provided by RefSeq, Jul 2008]

MAP2K6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K6	NM_002758.4 linkuse as main transcript	c.820C>T	p.Pro274Ser	missense_variant	10/12	ENST00000590474.7	NP_002749.2	P52564-1A8K3Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAP2K6	ENST00000590474.7 linkuse as main transcript	c.820C>T	p.Pro274Ser	missense_variant	10/12	1	NM_002758.4	ENSP00000468348.1	P52564-1
MAP2K6	ENST00000589647.5 linkuse as main transcript	c.652C>T	p.Pro218Ser	missense_variant	10/12	5		ENSP00000467213.1	P52564-2
MAP2K6	ENST00000359094.7 linkuse as main transcript	n.*551C>T		non_coding_transcript_exon_variant	10/12	5		ENSP00000351997.3	A0A0A0MRF7
MAP2K6	ENST00000359094.7 linkuse as main transcript	n.*551C>T		3_prime_UTR_variant	10/12	5		ENSP00000351997.3	A0A0A0MRF7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251300

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000474

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2023

The c.820C>T (p.P274S) alteration is located in exon 10 (coding exon 10) of the MAP2K6 gene. This alteration results from a C to T substitution at nucleotide position 820, causing the proline (P) at amino acid position 274 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;.

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Uncertain

0.75

Sift4G

Benign

0.23

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.55

MutPred

0.44

Gain of phosphorylation at P274 (P = 0.0376);.;.;

MVP

0.73

MPC

1.6

ClinPred

0.90

GERP RS

6.2

Varity_R

0.34

gMVP

0.78

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