5-168062044-CTTT-CT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001395460.1(TENM2):c.1310-5_1310-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,464,538 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (0 hom.)
• Consequence: TENM2 NM_001395460.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM2	NM_001395460.1	c.1310-5_1310-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000518659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM2	ENST00000518659.6	c.1310-5_1310-4del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001395460.1	P1

Frequencies

GnomAD3 genomes AF: 0.0000680 AC: 10 AN: 147050 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000748

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000449

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00237 AC: 3128 AN: 1317438 Hom.: 0 AF XY: 0.00267 AC XY: 1748 AN XY: 654368

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.00357

Gnomad4 ASJ exome AF: 0.00326

Gnomad4 EAS exome AF: 0.00977

Gnomad4 SAS exome AF: 0.00832

Gnomad4 FIN exome AF: 0.00427

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.0000816 AC: 12 AN: 147100 Hom.: 0 Cov.: 0 AF XY: 0.0000701 AC XY: 5 AN XY: 71358

Gnomad4 AFR AF: 0.0000746

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.000227

Gnomad4 NFE AF: 0.0000449

Gnomad4 OTH AF: 0.000492

Alfa AF: 0.0157 Hom.: 100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs11411759; hg19: chr5-167489049;