16-71283620-C-A

Position:

• chr16-71283620-C-A

Variant summary

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

The NM_018348.6(CMTR2):​c.2301G>T​(p.Gln767His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CMTR2 NM_018348.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0870

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=0.034897268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTR2	NM_018348.6	c.2301G>T	p.Gln767His	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.2301G>T	p.Gln767His	missense_variant	3/3	1	NM_018348.6	ENSP00000411148.2
CMTR2	ENST00000338099.9	c.2301G>T	p.Gln767His	missense_variant	3/3	1		ENSP00000337512.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458342 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725402

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Dec 13, 2023

The c.2301G>T (p.Q767H) 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 2301, causing the glutamine (Q) at amino acid position 767 to be replaced by a histidine (H). 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	0.093
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.6
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0032	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.084
Sift	Benign	0.040	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.0	B;B
Vest4		0.031
MutPred		0.12		Gain of disorder (P = 0.1671);Gain of disorder (P = 0.1671);
MVP		0.040
MPC		0.041
ClinPred		0.063	T
GERP RS		-0.54
Varity_R		0.033
gMVP		0.50

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: chr16-71317523;