rs2442802

Variant names:

• chr3-12566546-A-C
• rs2442802
• NM_014160.5:c.27-2329A>C

Variant summary

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

The NM_014160.5(MKRN2):​c.27-2329A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,988 control chromosomes in the GnomAD database, including 15,282 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 0.44 (15282 hom., cov: 32)
• Consequence: MKRN2 NM_014160.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671
• Publications: 12 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014160.5. 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
	MKRN2	NM_014160.5	MANE Select	c.27-2329A>C		intron	N/A	NP_054879.3
	MKRN2	NM_001271707.2		c.27-3525A>C		intron	N/A	NP_001258636.1	Q9H000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2	ENST00000170447.12	TSL:1 MANE Select	c.27-2329A>C		intron	N/A	ENSP00000170447.7	Q9H000-1
	MKRN2	ENST00000900946.1		c.347+2253A>C		intron	N/A	ENSP00000571005.1
	MKRN2	ENST00000900947.1		c.27-77A>C		intron	N/A	ENSP00000571006.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66343 AN: 151868 Hom.: 15263 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.437 AC: 66387 AN: 151988 Hom.: 15282 Cov.: 32 AF XY: 0.429 AC XY: 31861 AN XY: 74268

African (AFR) AF: 0.554 AC: 22954 AN: 41444

American (AMR) AF: 0.358 AC: 5472 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3466

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5182

South Asian (SAS) AF: 0.171 AC: 826 AN: 4828

European-Finnish (FIN) AF: 0.433 AC: 4557 AN: 10524

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29371 AN: 67954

Other (OTH) AF: 0.433 AC: 912 AN: 2108

Alfa AF: 0.422 Hom.: 7323

Bravo AF: 0.438

Asia WGS AF: 0.164 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.95
PhyloP100		0.67
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: rs2442802; hg19: chr3-12608045;