chr16-66580105-T-A

Variant names:

• chr16-66580105-T-A
• rs2290182
• NM_144673.3:c.365T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144673.3(CMTM2):​c.365T>A​(p.Ile122Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 0 publications found

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]

ENSG00000260650 (HGNC:58533):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM2	NM_144673.3	c.365T>A	p.Ile122Lys	missense_variant	Exon 2 of 4	ENST00000268595.3	NP_653274.1
CMTM2	NM_001199317.2	c.285+213T>A		intron_variant	Intron 1 of 2		NP_001186246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM2	ENST00000268595.3	c.365T>A	p.Ile122Lys	missense_variant	Exon 2 of 4	1	NM_144673.3	ENSP00000268595.2
CMTM2	ENST00000379486.6	c.285+213T>A		intron_variant	Intron 1 of 2	1		ENSP00000368800.2
ENSG00000260650	ENST00000568430.1	n.433A>T		non_coding_transcript_exon_variant	Exon 2 of 2	4
CMTM2	ENST00000569316.1	n.92-34T>A		intron_variant	Intron 1 of 3	5		ENSP00000454319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.0
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.019	D
Vest4		0.48
ClinPred		0.84	D
GERP RS		3.4
Varity_R		0.76
gMVP		0.71
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs2290182; hg19: chr16-66614008;