2-6865696-T-G

Position:

• chr2-6865696-T-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_207315.4(CMPK2):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 35)
• Consequence: CMPK2 NM_207315.4 initiator_codon
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.29

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]

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-6865696-T-G is Pathogenic according to our data. Variant chr2-6865696-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 3381200.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMPK2	NM_207315.4	c.1A>C	p.Met1?	initiator_codon_variant	1/5	ENST00000256722.10	NP_997198.2
CMPK2	NM_001256477.1	c.1A>C	p.Met1?	initiator_codon_variant	1/4		NP_001243406.1
CMPK2	NM_001256478.1	c.1A>C	p.Met1?	initiator_codon_variant	1/4		NP_001243407.1
CMPK2	NR_046236.2	n.210+730A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMPK2	ENST00000256722.10	c.1A>C	p.Met1?	initiator_codon_variant	1/5	1	NM_207315.4	ENSP00000256722.5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 35

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 10, AUTOSOMAL RECESSIVE Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.010	.;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.75	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.13	B;B;.
Vest4		0.71
MutPred		0.66		Gain of methylation at R5 (P = 0.1451);Gain of methylation at R5 (P = 0.1451);Gain of methylation at R5 (P = 0.1451);
MVP		0.54
ClinPred		0.56	D
GERP RS		3.7
Varity_R		0.93
gMVP		0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-7005827;