Variant 15-67748246-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145160.3(MAP2K5):c.1090G>C(p.Gly364Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAP2K5
NM_145160.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29

Variant links:

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

MAP2K5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30088487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAP2K5	NM_145160.3 linkuse as main transcript	c.1090G>C	p.Gly364Arg	missense_variant	18/22	ENST00000178640.10
MAP2K5	NM_002757.4 linkuse as main transcript	c.1060G>C	p.Gly354Arg	missense_variant	17/21
MAP2K5	NM_001206804.2 linkuse as main transcript	c.982G>C	p.Gly328Arg	missense_variant	18/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10 linkuse as main transcript	c.1090G>C	p.Gly364Arg	missense_variant	18/22	1	NM_145160.3	P1	Q13163-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455504

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 17, 2024

The c.1090G>C (p.G364R) alteration is located in exon 18 (coding exon 18) of the MAP2K5 gene. This alteration results from a G to C substitution at nucleotide position 1090, causing the glycine (G) at amino acid position 364 to be replaced by an arginine (R). 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

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;.;.

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.66

N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.053

T;T;T;T

Sift4G

Uncertain

0.054

T;T;T;T

Polyphen

0.99

D;P;.;D

Vest4

0.28

MutPred

0.62

Loss of ubiquitination at K361 (P = 0.0297);.;.;.;

MVP

0.84

MPC

2.2

ClinPred

0.90

GERP RS

6.0

Varity_R

0.23

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over