16-71284155-C-A

Position:

• chr16-71284155-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018348.6(CMTR2):​c.1766G>T​(p.Arg589Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CMTR2 NM_018348.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.14

Genes affected

CMTR2 (HGNC:25635): (cap methyltransferase 2) Enables mRNA (nucleoside-2'-O-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping and cap2 mRNA methylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07608807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTR2	NM_018348.6	c.1766G>T	p.Arg589Leu	missense_variant	3/3	ENST00000434935.7	NP_060818.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTR2	ENST00000434935.7	c.1766G>T	p.Arg589Leu	missense_variant	3/3	1	NM_018348.6	ENSP00000411148.2
CMTR2	ENST00000338099.9	c.1766G>T	p.Arg589Leu	missense_variant	3/3	1		ENSP00000337512.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.1766G>T (p.R589L) alteration is located in exon 3 (coding exon 1) of the CMTR2 gene. This alteration results from a G to T substitution at nucleotide position 1766, causing the arginine (R) at amino acid position 589 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0020
DANN	Benign	0.26
DEOGEN2	Benign	0.0033	T;T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.28	.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.081
Sift	Benign	0.65	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0020	B;B
Vest4		0.10
MutPred		0.53		Gain of ubiquitination at K592 (P = 0.042);Gain of ubiquitination at K592 (P = 0.042);
MVP		0.040
MPC		0.051
ClinPred		0.029	T
GERP RS		-12
Varity_R		0.020
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

Other links and lift over

dbSNP: rs763851216; hg19: chr16-71318058; COSMIC: COSV57604536; COSMIC: COSV57604536;