chr19-2059586-T-C

Variant names:

• chr19-2059586-T-C
• rs10404242
• ENST00000907124.1:c.-97+1326A>G

Variant summary

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

The ENST00000907124.1(MKNK2):​c.-97+1326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,158 control chromosomes in the GnomAD database, including 14,000 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 0.40 (14000 hom., cov: 34)
• Consequence: MKNK2 ENST00000907124.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 9 publications found

Genes affected

MKNK2 (HGNC:7111): (MAPK interacting serine/threonine kinase 2) This gene encodes a member of the calcium/calmodulin-dependent protein kinases (CAMK) Ser/Thr protein kinase family, which belongs to the protein kinase superfamily. This protein contains conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs, and an N-terminal polybasic region which binds importin A and the translation factor scaffold protein eukaryotic initiation factor 4G (eIF4G). This protein is one of the downstream kinases activated by mitogen-activated protein (MAP) kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation and malignant cell proliferation. In addition to eIF4E, this protein also interacts with von Hippel-Lindau tumor suppressor (VHL), ring-box 1 (Rbx1) and Cullin2 (Cul2), which are all components of the CBC(VHL) ubiquitin ligase E3 complex. Multiple alternatively spliced transcript variants have been found, but the full-length nature and biological activity of only two variants are determined. These two variants encode distinct isoforms which differ in activity and regulation, and in subcellular localization. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000907124.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKNK2	ENST00000907124.1		c.-97+1326A>G		intron	N/A	ENSP00000577183.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60963 AN: 152038 Hom.: 13951 Cov.: 34

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.405

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 61081 AN: 152158 Hom.: 14000 Cov.: 34 AF XY: 0.395 AC XY: 29354 AN XY: 74390

African (AFR) AF: 0.628 AC: 26095 AN: 41536

American (AMR) AF: 0.365 AC: 5575 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1323 AN: 5158

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2534 AN: 10608

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21272 AN: 67956

Other (OTH) AF: 0.411 AC: 867 AN: 2112

Alfa AF: 0.327 Hom.: 15314

Bravo AF: 0.422

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs10404242; hg19: chr19-2059585;