rs17069636

Positions:

• chr5-168022052-T-A
• chr5-168022052-T-C

Variant summary

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

The NM_001395460.1(TENM2):​c.1187-25375T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 152,358 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.019 (222 hom., cov: 33)
• Consequence: TENM2 NM_001395460.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM2	NM_001395460.1	c.1187-25375T>A		intron_variant		ENST00000518659.6	NP_001382389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM2	ENST00000518659.6	c.1187-25375T>A		intron_variant		5	NM_001395460.1	ENSP00000429430	P1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2819 AN: 152240 Hom.: 213 Cov.: 33

Gnomad AFR AF: 0.00400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.0205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0187 AC: 2843 AN: 152358 Hom.: 222 Cov.: 33 AF XY: 0.0212 AC XY: 1579 AN XY: 74506

Gnomad4 AFR AF: 0.00399

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.000915 Hom.: 1

Bravo AF: 0.0294

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.67

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: rs17069636; hg19: chr5-167449057;