chr2-206217239-G-T

Variant names:

• chr2-206217239-G-T
• rs2058708
• ENST00000407325.6:c.-148+570C>A

Variant summary

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

The ENST00000407325.6(CMKLR2):​c.-148+570C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,150 control chromosomes in the GnomAD database, including 545 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 0.078 (545 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CMKLR2 ENST00000407325.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.404
• Publications: 2 publications found

Genes affected

CMKLR2 (HGNC:4463): (chemerin chemokine-like receptor 2) Enables adipokinetic hormone binding activity and adipokinetic hormone receptor activity. Predicted to be involved in glucose homeostasis and neuropeptide signaling pathway. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CMKLR2-AS (HGNC:48602): (CMKLR2 antisense RNA) This gene is thought to produce a non-coding RNA. It is situated adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in the placenta. [provided by RefSeq, Nov 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMKLR2	NM_001098199.2	c.-144+570C>A		intron_variant	Intron 1 of 2		NP_001091669.1
CMKLR2	NM_001261452.2	c.-144+124C>A		intron_variant	Intron 2 of 3		NP_001248381.1
CMKLR2	NM_001261453.2	c.-148+124C>A		intron_variant	Intron 2 of 3		NP_001248382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMKLR2	ENST00000407325.6	c.-148+570C>A		intron_variant	Intron 1 of 2	1		ENSP00000384345.2
CMKLR2	ENST00000437420.5	c.-144+124C>A		intron_variant	Intron 2 of 3	1		ENSP00000397535.1
CMKLR2	ENST00000411719.1	c.-144+570C>A		intron_variant	Intron 1 of 2	3		ENSP00000404861.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11811 AN: 152032 Hom.: 545 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0776 AC: 11813 AN: 152150 Hom.: 545 Cov.: 32 AF XY: 0.0780 AC XY: 5806 AN XY: 74392

African (AFR) AF: 0.0444 AC: 1842 AN: 41516

American (AMR) AF: 0.0579 AC: 885 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3468

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5168

South Asian (SAS) AF: 0.0955 AC: 460 AN: 4818

European-Finnish (FIN) AF: 0.123 AC: 1298 AN: 10592

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6747 AN: 67984

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0905 Hom.: 1313

Bravo AF: 0.0694

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.67
PhyloP100		0.40
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: rs2058708; hg19: chr2-207081963;