Variant 22-50603906-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012324.6(MAPK8IP2):c.607G>T(p.Gly203Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,537,500 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 4 hom. )

Consequence

MAPK8IP2
NM_012324.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

MAPK8IP2 (HGNC:6883): (mitogen-activated protein kinase 8 interacting protein 2) This gene encodes a scaffold protein that is thought to be involved in the regulation of the c-Jun amino-terminal kinase signaling pathway. This protein has been shown to interact with and regulate the activity of MAPK8/JNK1 and MAP2K7/MKK7 kinases. [provided by RefSeq, Jun 2017]

MAPK8IP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008943081).

BS2

High AC in GnomAd4 at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAPK8IP2	NM_012324.6 linkuse as main transcript	c.607G>T	p.Gly203Cys	missense_variant	5/12	ENST00000329492.6	NP_036456.1
MAPK8IP2	XM_011530679.3 linkuse as main transcript	c.610G>T	p.Gly204Cys	missense_variant	5/12		XP_011528981.1
MAPK8IP2	XM_011530680.3 linkuse as main transcript	c.542-46G>T		intron_variant			XP_011528982.1
MAPK8IP2	XM_011530681.3 linkuse as main transcript	c.542-67G>T		intron_variant			XP_011528983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8IP2	ENST00000329492.6 linkuse as main transcript	c.607G>T	p.Gly203Cys	missense_variant	5/12	1	NM_012324.6	ENSP00000330572	P1	Q13387-1
MAPK8IP2	ENST00000008876.7 linkuse as main transcript	n.526G>T		non_coding_transcript_exon_variant	3/10	1

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00187

AC:

246

AN:

131382

Hom.:

AF XY:

0.00155

AC XY:

112

AN XY:

72038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0102

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:

0.00

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000241

AC:

334

AN:

1385284

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

153

AN XY:

683234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00897

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:

0.00

Gnomad4 OTH exome

AF:

0.000330

GnomAD4 genome

AF:

0.000624

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.00127

ExAC

AF:

0.000164

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

Aug 09, 2021

The c.607G>T (p.G203C) alteration is located in exon 5 (coding exon 5) of the MAPK8IP2 gene. This alteration results from a G to T substitution at nucleotide position 607, causing the glycine (G) at amino acid position 203 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

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Uncertain

0.015

Sift4G

Benign

0.13

Polyphen

0.95

Vest4

0.31

MutPred

0.13

Gain of catalytic residue at P202 (P = 0.0046);

MVP

0.51

ClinPred

0.082

GERP RS

3.3

Varity_R

0.20

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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