rs140511

Variant names:

• chr22-50604084-C-CG
• rs140511
• NM_012324.6:c.786dupG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012324.6(MAPK8IP2):​c.786dupG​(p.Arg263AlafsTer182) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPK8IP2 NM_012324.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012324.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8IP2	NM_012324.6	MANE Select	c.786dupG	p.Arg263AlafsTer182	frameshift	Exon 5 of 12	NP_036456.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8IP2	ENST00000329492.6	TSL:1 MANE Select	c.786dupG	p.Arg263AlafsTer182	frameshift	Exon 5 of 12	ENSP00000330572.4
	MAPK8IP2	ENST00000008876.7	TSL:1	n.705dupG		non_coding_transcript_exon	Exon 3 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 1.00 AC: 141596 AN: 141598 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 1.00 Hom.: 6675

Asia WGS AF: 1.00 AC: 3472 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140511; hg19: chr22-51042513;