Variant 2-6865686-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207315.4(CMPK2):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000923 in 1,300,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

CMPK2
NM_207315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.543

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:

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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=0.058332413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMPK2	NM_207315.4 link	c.11C>T	p.Ala4Val	missense_variant	1/5	ENST00000256722.10	NP_997198.2	Q5EBM0-1
CMPK2	NM_001256477.1 link	c.11C>T	p.Ala4Val	missense_variant	1/4		NP_001243406.1	Q5EBM0-4
CMPK2	NM_001256478.1 link	c.11C>T	p.Ala4Val	missense_variant	1/4		NP_001243407.1	Q5EBM0-3
CMPK2	NR_046236.2 link	n.210+740C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMPK2	ENST00000256722.10 link	c.11C>T	p.Ala4Val	missense_variant	1/5	1	NM_207315.4	ENSP00000256722.5		Q5EBM0-1

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000522

AC:

AN:

1148328

Hom.:

Cov.:

AF XY:

0.00000542

AC XY:

AN XY:

553892

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000232

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151722

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

ExAC

AF:

0.000261

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

Aug 04, 2023

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the CMPK2 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

.;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.55

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.044

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.077

B;B;.

Vest4

0.036

MutPred

0.29

Loss of methylation at R5 (P = 0.0956);Loss of methylation at R5 (P = 0.0956);Loss of methylation at R5 (P = 0.0956);

MVP

0.20

MPC

0.34

ClinPred

0.089

GERP RS

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.37

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