16-66588024-G-A

Position:

• chr16-66588024-G-A

Variant summary

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

The NM_144673.3(CMTM2):​c.652G>A​(p.Gly218Arg) 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: 33)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.00

Genes affected

CMTM2 (HGNC:19173): (CKLF like MARVEL transmembrane domain containing 2) This gene belongs to the chemokine-like factor gene superfamily, a novel family that links the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development. [provided by RefSeq, Jul 2008]

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=0.061728925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM2	NM_144673.3	c.652G>A	p.Gly218Arg	missense_variant	4/4	ENST00000268595.3	NP_653274.1
CMTM2	NM_001199317.2	c.493G>A	p.Gly165Arg	missense_variant	3/3		NP_001186246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM2	ENST00000268595.3	c.652G>A	p.Gly218Arg	missense_variant	4/4	1	NM_144673.3	ENSP00000268595.2
CMTM2	ENST00000379486.6	c.493G>A	p.Gly165Arg	missense_variant	3/3	1		ENSP00000368800.2
CMTM2	ENST00000532362.1	n.296G>A		non_coding_transcript_exon_variant	2/2	2
CMTM2	ENST00000569316.1	n.*189G>A		downstream_gene_variant		5		ENSP00000454319.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 14, 2023

The c.652G>A (p.G218R) alteration is located in exon 4 (coding exon 4) of the CMTM2 gene. This alteration results from a G to A substitution at nucleotide position 652, causing the glycine (G) at amino acid position 218 to be replaced by an arginine (R). 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	0.19
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.085
DANN	Benign	0.62
DEOGEN2	Benign	0.0018	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.039
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.048	D;D
Polyphen		0.018	.;B
Vest4		0.086
MutPred		0.18		.;Gain of MoRF binding (P = 0.0244);
MVP		0.27
MPC		0.24
ClinPred		0.082	T
GERP RS		-6.4
Varity_R		0.072
gMVP		0.15

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: chr16-66621927;