2-6865636-C-G

Position:

chr2-6865636-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207315.4(CMPK2):c.61G>C(p.Gly21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,355,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CMPK2
NM_207315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.466

Variant links:

Genes affected

CMPK2 (HGNC:27015): (cytidine/uridine monophosphate kinase 2) This gene encodes one of the enzymes in the nucleotide synthesis salvage pathway that may participate in terminal differentiation of monocytic cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

CMPK2 links:

RSAD2 (HGNC:30908): (radical S-adenosyl methionine domain containing 2) The protein encoded by this gene is an interferon-inducible antiviral protein that belongs to the S-adenosyl-L-methionine (SAM) superfamily of enzymes. The protein plays a role in cellular antiviral response and innate immune signaling. Antiviral effects result from inhibition of viral RNA replication, interference in the secretory pathway, binding to viral proteins and dysregulation of cellular lipid metabolism. The protein has been found to inhibit both DNA and RNA viruses, including influenza virus, human immunodeficiency virus (HIV-1) and Zika virus. [provided by RefSeq, Sep 2020]

RSAD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0055209696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMPK2	NM_207315.4 link	c.61G>C	p.Gly21Arg	missense_variant	1/5	ENST00000256722.10	NP_997198.2	Q5EBM0-1
CMPK2	NM_001256477.1 link	c.61G>C	p.Gly21Arg	missense_variant	1/4		NP_001243406.1	Q5EBM0-4
CMPK2	NM_001256478.1 link	c.61G>C	p.Gly21Arg	missense_variant	1/4		NP_001243407.1	Q5EBM0-3
CMPK2	NR_046236.2 link	n.210+790G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMPK2	ENST00000256722.10 link	c.61G>C	p.Gly21Arg	missense_variant	1/5	1	NM_207315.4	ENSP00000256722.5		Q5EBM0-1

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000295

AC:

AN:

30554

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

18634

show subpopulations

Gnomad AFR exome

AF:

0.00242

Gnomad AMR exome

AF:

0.000223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000252

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

162

AN:

1203852

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

588672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000836

Gnomad4 AMR exome

AF:

0.0000707

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000315

Gnomad4 FIN exome

AF:

0.0000704

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.0000824

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000125

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.61G>C (p.G21R) alteration is located in exon 1 (coding exon 1) of the CMPK2 gene. This alteration results from a G to C substitution at nucleotide position 61, causing the glycine (G) at amino acid position 21 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.028

.;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.52

T;T;T

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.55

N;N;N

REVEL

Benign

0.026

Sift

Uncertain

0.010

D;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.080

MutPred

0.39

Gain of MoRF binding (P = 0.0224);Gain of MoRF binding (P = 0.0224);Gain of MoRF binding (P = 0.0224);

MVP

0.30

MPC

0.40

ClinPred

0.011

GERP RS

0.80

Varity_R

0.11

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over