16-66587988-A-G

Position:

• chr16-66587988-A-G

Variant summary

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

The NM_144673.3(CMTM2):​c.616A>G​(p.Lys206Glu) 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. 13/21 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: 3.49

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 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=0.23683897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM2	NM_144673.3	c.616A>G	p.Lys206Glu	missense_variant	4/4	ENST00000268595.3	NP_653274.1
CMTM2	NM_001199317.2	c.457A>G	p.Lys153Glu	missense_variant	3/3		NP_001186246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM2	ENST00000268595.3	c.616A>G	p.Lys206Glu	missense_variant	4/4	1	NM_144673.3	ENSP00000268595.2
CMTM2	ENST00000379486.6	c.457A>G	p.Lys153Glu	missense_variant	3/3	1		ENSP00000368800.2
CMTM2	ENST00000532362.1	n.260A>G		non_coding_transcript_exon_variant	2/2	2
CMTM2	ENST00000569316.1	n.*153A>G		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

Jun 02, 2023

The c.616A>G (p.K206E) alteration is located in exon 4 (coding exon 4) of the CMTM2 gene. This alteration results from a A to G substitution at nucleotide position 616, causing the lysine (K) at amino acid position 206 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	0.34
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	0.052
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.20
Sift	Uncertain	0.020	D;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	.;D
Vest4		0.37
MutPred		0.36		.;Loss of MoRF binding (P = 0.0073);
MVP		0.69
MPC		0.90
ClinPred		0.92	D
GERP RS		2.9
Varity_R		0.14
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-66621891;