22-50606680-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_012324.6(MAPK8IP2):c.2147C>T(p.Thr716Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MAPK8IP2
NM_012324.6 missense
NM_012324.6 missense
Scores
6
7
3
Clinical Significance
Conservation
PhyloP100: 4.89
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.799
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK8IP2 | NM_012324.6 | c.2147C>T | p.Thr716Ile | missense_variant | 9/12 | ENST00000329492.6 | |
MAPK8IP2 | XM_011530679.3 | c.2150C>T | p.Thr717Ile | missense_variant | 9/12 | ||
MAPK8IP2 | XM_011530680.3 | c.2036C>T | p.Thr679Ile | missense_variant | 9/12 | ||
MAPK8IP2 | XM_011530681.3 | c.2015C>T | p.Thr672Ile | missense_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK8IP2 | ENST00000329492.6 | c.2147C>T | p.Thr716Ile | missense_variant | 9/12 | 1 | NM_012324.6 | P1 | |
MAPK8IP2 | ENST00000008876.7 | n.2066C>T | non_coding_transcript_exon_variant | 7/10 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1445448Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 717390
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1445448
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
717390
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
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 | Sep 16, 2021 | The c.2147C>T (p.T716I) alteration is located in exon 9 (coding exon 9) of the MAPK8IP2 gene. This alteration results from a C to T substitution at nucleotide position 2147, causing the threonine (T) at amino acid position 716 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
T
REVEL
Uncertain
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of phosphorylation at T716 (P = 0.0423);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.