22-50603225-C-A

Position:

• chr22-50603225-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012324.6(MAPK8IP2):​c.174C>A​(p.Asp58Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPK8IP2 NM_012324.6 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.826

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20176369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK8IP2	NM_012324.6	c.174C>A	p.Asp58Glu	missense_variant, splice_region_variant	3/12	ENST00000329492.6	NP_036456.1
MAPK8IP2	XM_011530679.3	c.174C>A	p.Asp58Glu	missense_variant, splice_region_variant	3/12		XP_011528981.1
MAPK8IP2	XM_011530680.3	c.174C>A	p.Asp58Glu	missense_variant, splice_region_variant	3/12		XP_011528982.1
MAPK8IP2	XM_011530681.3	c.174C>A	p.Asp58Glu	missense_variant, splice_region_variant	3/12		XP_011528983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8IP2	ENST00000329492.6	c.174C>A	p.Asp58Glu	missense_variant, splice_region_variant	3/12	1	NM_012324.6	ENSP00000330572.4
MAPK8IP2	ENST00000008876.7	n.93C>A		non_coding_transcript_exon_variant	1/10	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.174C>A (p.D58E) alteration is located in exon 3 (coding exon 3) of the MAPK8IP2 gene. This alteration results from a C to A substitution at nucleotide position 174, causing the aspartic acid (D) at amino acid position 58 to be replaced by a glutamic acid (E). 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	0.35
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.067
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Benign	0.096	T
Sift4G	Benign	0.18	T
Polyphen		0.43	B
Vest4		0.49
MutPred		0.096		Gain of methylation at K57 (P = 0.0977);
MVP		0.62
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-51041654;