Variant 19-7909883-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_145185.4(MAP2K7):c.253C>T(p.Arg85Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,373,058 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: 0.000012 ( 0 hom. )

Consequence

MAP2K7
NM_145185.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

MAP2K7 (HGNC:6847): (mitogen-activated protein kinase kinase 7) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2,MAP3K3/MEKK5, and MAP4K2/GCK. This kinase is involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MAP2K7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3507526).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAP2K7	NM_145185.4 linkuse as main transcript	c.253C>T	p.Arg85Cys	missense_variant	2/11	ENST00000397979.4	NP_660186.1
MAP2K7	NM_001297555.2 linkuse as main transcript	c.301C>T	p.Arg101Cys	missense_variant	3/12		NP_001284484.1
MAP2K7	NM_001297556.2 linkuse as main transcript	c.253C>T	p.Arg85Cys	missense_variant	2/11		NP_001284485.1
MAP2K7	XM_006722800.3 linkuse as main transcript	c.301C>T	p.Arg101Cys	missense_variant	3/12		XP_006722863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K7	ENST00000397979.4 linkuse as main transcript	c.253C>T	p.Arg85Cys	missense_variant	2/11	1	NM_145185.4	ENSP00000381066	P4	O14733-1
MAP2K7	ENST00000397983.7 linkuse as main transcript	c.301C>T	p.Arg101Cys	missense_variant	3/12	1		ENSP00000381070	A1	O14733-3
MAP2K7	ENST00000397981.7 linkuse as main transcript	c.253C>T	p.Arg85Cys	missense_variant	2/11	1		ENSP00000381068		O14733-4
MAP2K7	ENST00000468058.1 linkuse as main transcript	n.318C>T		non_coding_transcript_exon_variant	2/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000789

AC:

AN:

126774

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000991

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1373058

Hom.:

Cov.:

AF XY:

0.0000119

AC XY:

AN XY:

674802

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000656

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000845

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000195

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

Apr 17, 2023

The c.253C>T (p.R85C) alteration is located in exon 2 (coding exon 2) of the MAP2K7 gene. This alteration results from a C to T substitution at nucleotide position 253, causing the arginine (R) at amino acid position 85 to be replaced by a cysteine (C). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

.;.;D

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.011

D;D;D

Sift4G

Uncertain

0.034

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.22

MutPred

0.27

Gain of catalytic residue at P84 (P = 0.0134);.;Gain of catalytic residue at P84 (P = 0.0134);

MVP

0.65

MPC

1.5

ClinPred

0.96

GERP RS

5.0

Varity_R

0.33

gMVP

0.40

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