16-71283773-G-C

Position:

• chr16-71283773-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018348.6(CMTR2):​c.2148C>G​(p.Asp716Glu) 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: -1.06

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 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=0.032513916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTR2	NM_018348.6	c.2148C>G	p.Asp716Glu	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.2148C>G	p.Asp716Glu	missense_variant	3/3	1	NM_018348.6	ENSP00000411148.2
CMTR2	ENST00000338099.9	c.2148C>G	p.Asp716Glu	missense_variant	3/3	1		ENSP00000337512.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 16, 2024

The c.2148C>G (p.D716E) alteration is located in exon 3 (coding exon 1) of the CMTR2 gene. This alteration results from a C to G substitution at nucleotide position 2148, causing the aspartic acid (D) at amino acid position 716 to be replaced by a glutamic acid (E). 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	0.097
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.015
DANN	Benign	0.66
DEOGEN2	Benign	0.0030	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.49	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.0090
Sift	Benign	0.35	T;T
Sift4G	Benign	0.94	T;T
Polyphen		0.0020	B;B
Vest4		0.048
MutPred		0.29		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.061
MPC		0.041
ClinPred		0.091	T
GERP RS		-1.7
Varity_R		0.035
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71317676;