Variant 15-67806734-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145160.3(MAP2K5):c.1331A>G(p.Gln444Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,401,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MAP2K5
NM_145160.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20753655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAP2K5	NM_145160.3 linkuse as main transcript	c.1331A>G	p.Gln444Arg	missense_variant	22/22	ENST00000178640.10
MAP2K5	NM_002757.4 linkuse as main transcript	c.1301A>G	p.Gln434Arg	missense_variant	21/21
MAP2K5	NM_001206804.2 linkuse as main transcript	c.1223A>G	p.Gln408Arg	missense_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10 linkuse as main transcript	c.1331A>G	p.Gln444Arg	missense_variant	22/22	1	NM_145160.3	P1	Q13163-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1401672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692072

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:

9.24e-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

Nov 19, 2022

The c.1331A>G (p.Q444R) alteration is located in exon 22 (coding exon 22) of the MAP2K5 gene. This alteration results from a A to G substitution at nucleotide position 1331, causing the glutamine (Q) at amino acid position 444 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

Benign

0.079

BayesDel_addAF

Benign

0.0046

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.;.;.

Eigen

Benign

0.016

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.4

L;.;.;.

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.69

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.037

B;B;.;B

Vest4

0.24

MutPred

0.26

Gain of MoRF binding (P = 0.0199);.;.;.;

MVP

0.78

MPC

1.1

ClinPred

0.52

GERP RS

5.5

Varity_R

0.057

gMVP

0.30

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

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