rs2255648

Positions:

• chr3-12557464-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014160.5(MKRN2):​c.26+288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,216 control chromosomes in the GnomAD database, including 25,962 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 0.56 (25962 hom., cov: 34)
• Consequence: MKRN2 NM_014160.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

MKRN2 (HGNC:7113): (makorin ring finger protein 2) This gene encodes a probable E3 ubiquitin ligase containing several zinc finger domains, that is a member of the makorin RING zinc-finger protein family. This gene overlaps the v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1) gene in an antisense orientation and may have a co-regulatory function with RAF1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

MKRN2OS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKRN2	NM_014160.5	c.26+288A>G		intron_variant		ENST00000170447.12	NP_054879.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKRN2	ENST00000170447.12	c.26+288A>G		intron_variant		1	NM_014160.5	ENSP00000170447.7

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84751 AN: 152098 Hom.: 25923 Cov.: 34

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.557 AC: 84840 AN: 152216 Hom.: 25962 Cov.: 34 AF XY: 0.548 AC XY: 40809 AN XY: 74434

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.0986

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.528

Alfa AF: 0.507 Hom.: 17091

Bravo AF: 0.576

Asia WGS AF: 0.226 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.74

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: rs2255648; hg19: chr3-12598963;