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GeneBe

22-50604457-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_012324.6(MAPK8IP2):c.1158G>C(p.Pro386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,375,450 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 8 hom. )

Consequence

MAPK8IP2
NM_012324.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.615
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-50604457-G-C is Benign according to our data. Variant chr22-50604457-G-C is described in ClinVar as [Benign]. Clinvar id is 780679.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.615 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00668 (999/149534) while in subpopulation AFR AF= 0.0233 (951/40778). AF 95% confidence interval is 0.0221. There are 10 homozygotes in gnomad4. There are 488 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 993 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAPK8IP2NM_012324.6 linkuse as main transcriptc.1158G>C p.Pro386= synonymous_variant 5/12 ENST00000329492.6
MAPK8IP2XM_011530679.3 linkuse as main transcriptc.1161G>C p.Pro387= synonymous_variant 5/12
MAPK8IP2XM_011530680.3 linkuse as main transcriptc.1047G>C p.Pro349= synonymous_variant 5/12
MAPK8IP2XM_011530681.3 linkuse as main transcriptc.1026G>C p.Pro342= synonymous_variant 5/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAPK8IP2ENST00000329492.6 linkuse as main transcriptc.1158G>C p.Pro386= synonymous_variant 5/121 NM_012324.6 P1Q13387-1
MAPK8IP2ENST00000008876.7 linkuse as main transcriptn.1077G>C non_coding_transcript_exon_variant 3/101

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00665
AC:
993
AN:
149432
Hom.:
9
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0232
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00245
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:
0.0000744
Gnomad OTH
AF:
0.00293
GnomAD3 exomes
AF:
0.000864
AC:
12
AN:
13884
Hom.:
0
AF XY:
0.000362
AC XY:
3
AN XY:
8280
show subpopulations
Gnomad AFR exome
AF:
0.0268
Gnomad AMR exome
AF:
0.000668
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:
0.000193
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000580
AC:
711
AN:
1225916
Hom.:
8
Cov.:
34
AF XY:
0.000498
AC XY:
296
AN XY:
594126
show subpopulations
Gnomad4 AFR exome
AF:
0.0237
Gnomad4 AMR exome
AF:
0.00182
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000706
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000140
Gnomad4 OTH exome
AF:
0.00164
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00668
AC:
999
AN:
149534
Hom.:
10
Cov.:
33
AF XY:
0.00668
AC XY:
488
AN XY:
73076
show subpopulations
Gnomad4 AFR
AF:
0.0233
Gnomad4 AMR
AF:
0.00245
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000744
Gnomad4 OTH
AF:
0.00290
Alfa
AF:
0.00465
Hom.:
0
Bravo
AF:
0.00764

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 13, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.46
Dann
Benign
0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs553840616; hg19: chr22-51042885; API