5-167284857-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_001395460.1(TENM2):c.20G>A(p.Arg7Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,551,342 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (41 hom.)
• Consequence: TENM2 NM_001395460.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.60

Genes affected

TENM2 (HGNC:29943): (teneurin transmembrane protein 2) Enables cell adhesion molecule binding activity and signaling receptor binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; and retrograde trans-synaptic signaling by trans-synaptic protein complex. Located in cell-cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, TENM2
• BP4: Computational evidence support a benign effect (MetaRNN=0.008473635).
• BP6: Variant 5-167284857-G-A is Benign according to our data. Variant chr5-167284857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 710 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM2	NM_001395460.1	c.20G>A	p.Arg7Gln	missense_variant	3/31	ENST00000518659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM2	ENST00000518659.6	c.20G>A	p.Arg7Gln	missense_variant	3/31	5	NM_001395460.1	P1
TENM2	ENST00000695884.1	n.672G>A		non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 710 AN: 152082 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00795

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00432 AC: 679 AN: 157014 Hom.: 3 AF XY: 0.00461 AC XY: 383 AN XY: 83076

Gnomad AFR exome AF: 0.000993

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00290

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00768

Gnomad OTH exome AF: 0.00657

GnomAD4 exome AF: 0.00659 AC: 9218 AN: 1399142 Hom.: 41 Cov.: 31 AF XY: 0.00651 AC XY: 4494 AN XY: 690044

Gnomad4 AFR exome AF: 0.000855

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00461

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00325

Gnomad4 FIN exome AF: 0.00203

Gnomad4 NFE exome AF: 0.00773

Gnomad4 OTH exome AF: 0.00531

GnomAD4 genome AF: 0.00466 AC: 709 AN: 152200 Hom.: 1 Cov.: 33 AF XY: 0.00466 AC XY: 347 AN XY: 74418

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00794

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00741 Hom.: 1

Bravo AF: 0.00467

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00597 AC: 23

ExAC AF: 0.00414 AC: 106

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TENM2: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.080
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.0028	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.0085	T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.79	N
REVEL	Uncertain	0.58
Sift	Uncertain	0.011	D
Sift4G	Benign	0.070	T
Polyphen		0.99	D
Vest4		0.31
MVP		0.32
MPC		1.2
ClinPred		0.036	T
GERP RS		5.2
Varity_R		0.24

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: rs115605129; hg19: chr5-166711862;