22-50606662-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012324.6(MAPK8IP2):c.2129C>T(p.Ala710Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,439,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
MAPK8IP2
NM_012324.6 missense
NM_012324.6 missense
Scores
5
6
5
Clinical Significance
Conservation
PhyloP100: 6.07
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPK8IP2 | NM_012324.6 | c.2129C>T | p.Ala710Val | missense_variant | 9/12 | ENST00000329492.6 | |
MAPK8IP2 | XM_011530679.3 | c.2132C>T | p.Ala711Val | missense_variant | 9/12 | ||
MAPK8IP2 | XM_011530680.3 | c.2018C>T | p.Ala673Val | missense_variant | 9/12 | ||
MAPK8IP2 | XM_011530681.3 | c.1997C>T | p.Ala666Val | missense_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPK8IP2 | ENST00000329492.6 | c.2129C>T | p.Ala710Val | missense_variant | 9/12 | 1 | NM_012324.6 | P1 | |
MAPK8IP2 | ENST00000008876.7 | n.2048C>T | non_coding_transcript_exon_variant | 7/10 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 6.95e-7 AC: 1AN: 1439168Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1AN XY: 713720
GnomAD4 exome
AF:
AC:
1
AN:
1439168
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
713720
Gnomad4 AFR 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 | Dec 27, 2022 | The c.2129C>T (p.A710V) 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 2129, causing the alanine (A) at amino acid position 710 to be replaced by a valine (V). 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
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
REVEL
Benign
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.1198);
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.