rs2238834

Positions:

• chr22-50601349-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK8IP2	NM_012324.6	c.66-440C>A		intron_variant		ENST00000329492.6	NP_036456.1
MAPK8IP2	XM_011530679.3	c.66-440C>A		intron_variant			XP_011528981.1
MAPK8IP2	XM_011530680.3	c.66-440C>A		intron_variant			XP_011528982.1
MAPK8IP2	XM_011530681.3	c.66-440C>A		intron_variant			XP_011528983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8IP2	ENST00000329492.6	c.66-440C>A		intron_variant		1	NM_012324.6	ENSP00000330572	P1
CHKB	ENST00000463053.1	n.107G>T		non_coding_transcript_exon_variant	1/7	3

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

Gnomad4 AFR exome AF: 0.0876

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.374

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

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.323

Alfa AF: 0.399 Hom.: 18129

Bravo AF: 0.303

Asia WGS AF: 0.301 AC: 1047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.5
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs2238834; hg19: chr22-51039778;