chr22-50603906-G-T
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
NM_012324.6 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 1.42
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]
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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 GnomAd at 92 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK8IP2 | NM_012324.6 | c.607G>T | p.Gly203Cys | missense_variant | 5/12 | ENST00000329492.6 | |
MAPK8IP2 | XM_011530679.3 | c.610G>T | p.Gly204Cys | missense_variant | 5/12 | ||
MAPK8IP2 | XM_011530680.3 | c.542-46G>T | intron_variant | ||||
MAPK8IP2 | XM_011530681.3 | c.542-67G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK8IP2 | ENST00000329492.6 | c.607G>T | p.Gly203Cys | missense_variant | 5/12 | 1 | NM_012324.6 | P1 | |
MAPK8IP2 | ENST00000008876.7 | n.526G>T | non_coding_transcript_exon_variant | 3/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000605 AC: 92AN: 152096Hom.: 1 Cov.: 33
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?
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GnomAD3 exomes AF: 0.00187 AC: 246AN: 131382Hom.: 1 AF XY: 0.00155 AC XY: 112AN XY: 72038
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GnomAD4 exome AF: 0.000241 AC: 334AN: 1385284Hom.: 4 Cov.: 34 AF XY: 0.000224 AC XY: 153AN XY: 683234
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GnomAD4 genome ? AF: 0.000624 AC: 95AN: 152216Hom.: 1 Cov.: 33 AF XY: 0.000712 AC XY: 53AN XY: 74420
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at P202 (P = 0.0046);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at