rs2238834

Variant names:

• chr22-50601349-C-A
• rs2238834
• NM_012324.6:c.66-440C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012324.6(MAPK8IP2):​c.66-440C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 171,542 control chromosomes in the GnomAD database, including 10,693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9209 hom., cov: 32)
  • Exomes 𝑓: 0.37 (1484 hom.)
• Consequence: MAPK8IP2 NM_012324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 13 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]

CHKB (HGNC:1938): (choline kinase beta) Choline kinase (CK) and ethanolamine kinase (EK) catalyze the phosphorylation of choline/ethanolamine to phosphocholine/phosphoethanolamine. This is the first enzyme in the biosynthesis of phosphatidylcholine/phosphatidylethanolamine in all animal cells. The highly purified CKs from mammalian sources and their recombinant gene products have been shown to have EK activity also, indicating that both activities reside on the same protein. The choline kinase-like protein encoded by CHKL belongs to the choline/ethanolamine kinase family; however, its exact function is not known. Read-through transcripts are expressed from this locus that include exons from the downstream CPT1B locus. [provided by RefSeq, Jun 2009]

CHKB Gene-Disease associations (from GenCC):

• megaconial type congenital muscular dystrophy

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

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.66-440C>A		intron	N/A	NP_036456.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8IP2	ENST00000329492.6	TSL:1 MANE Select	c.66-440C>A		intron	N/A	ENSP00000330572.4
	CHKB	ENST00000463053.1	TSL:3	n.107G>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48644 AN: 151948 Hom.: 9213 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.372 AC: 7250 AN: 19476 Hom.: 1484 Cov.: 0 AF XY: 0.366 AC XY: 3796 AN XY: 10378

African (AFR) AF: 0.0876 AC: 75 AN: 856

American (AMR) AF: 0.366 AC: 966 AN: 2640

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 111 AN: 340

East Asian (EAS) AF: 0.279 AC: 389 AN: 1396

South Asian (SAS) AF: 0.344 AC: 801 AN: 2326

European-Finnish (FIN) AF: 0.444 AC: 200 AN: 450

Middle Eastern (MID) AF: 0.296 AC: 16 AN: 54

European-Non Finnish (NFE) AF: 0.414 AC: 4352 AN: 10504

Other (OTH) AF: 0.374 AC: 340 AN: 910

GnomAD4 genome AF: 0.320 AC: 48644 AN: 152066 Hom.: 9209 Cov.: 32 AF XY: 0.324 AC XY: 24093 AN XY: 74344

African (AFR) AF: 0.111 AC: 4616 AN: 41546

American (AMR) AF: 0.350 AC: 5348 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3462

East Asian (EAS) AF: 0.302 AC: 1560 AN: 5158

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4824

European-Finnish (FIN) AF: 0.464 AC: 4908 AN: 10586

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28068 AN: 67906

Other (OTH) AF: 0.323 AC: 680 AN: 2104

Alfa AF: 0.394 Hom.: 27889

Bravo AF: 0.303

Asia WGS AF: 0.301 AC: 1047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.5
DANN	Benign	0.84
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2238834; hg19: chr22-51039778;