rs2290182

Positions:

• chr16-66580105-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144673.3(CMTM2):​c.365T>C​(p.Ile122Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,614,022 control chromosomes in the GnomAD database, including 18,379 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2720 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15659 hom.)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058350563).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM2	NM_144673.3	c.365T>C	p.Ile122Thr	missense_variant	2/4	ENST00000268595.3
CMTM2	NM_001199317.2	c.285+213T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM2	ENST00000268595.3	c.365T>C	p.Ile122Thr	missense_variant	2/4	1	NM_144673.3	P1
CMTM2	ENST00000379486.6	c.285+213T>C		intron_variant		1
	ENST00000568430.1	n.433A>G		non_coding_transcript_exon_variant	2/2	4
CMTM2	ENST00000569316.1	c.92-34T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26214 AN: 152068 Hom.: 2717 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0956

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.180 AC: 45384 AN: 251484 Hom.: 5127 AF XY: 0.174 AC XY: 23679 AN XY: 135916

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.0995

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.132 AC: 192696 AN: 1461836 Hom.: 15659 Cov.: 34 AF XY: 0.133 AC XY: 96931 AN XY: 727230

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.172 AC: 26246 AN: 152186 Hom.: 2720 Cov.: 32 AF XY: 0.173 AC XY: 12865 AN XY: 74434

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.0956

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.157

Alfa AF: 0.132 Hom.: 3892

Bravo AF: 0.190

TwinsUK AF: 0.107 AC: 396

ALSPAC AF: 0.117 AC: 449

ESP6500AA AF: 0.266 AC: 1173

ESP6500EA AF: 0.113 AC: 973

ExAC AF: 0.180 AC: 21834

Asia WGS AF: 0.265 AC: 920 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.063
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.054	T
Polyphen		0.058	B
Vest4		0.070
MPC		0.34
ClinPred		0.026	T
GERP RS		3.4
Varity_R		0.14
gMVP		0.41

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: rs2290182; hg19: chr16-66614008; COSMIC: COSV51749466; COSMIC: COSV51749466;