Genetic Variant TENM2:c.1310-6_1310-4dupTTT (chr5-168062044-C-CTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001395460.1(TENM2):c.1310-6_1310-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000088 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0010 ( 0 hom. )

Consequence

TENM2
NM_001395460.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.806

Publications

1 publications found

Variant links:

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]

TENM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395460.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TENM2	NM_001395460.1	MANE Select	c.1310-6_1310-4dupTTT	splice_region intron	N/A	NP_001382389.1
TENM2	NM_001122679.2		c.1310-6_1310-4dupTTT	splice_region intron	N/A	NP_001116151.1
TENM2	NM_001368145.1		c.854-6_854-4dupTTT	splice_region intron	N/A	NP_001355074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TENM2	ENST00000518659.6	TSL:5 MANE Select	c.1310-16_1310-15insTTT	intron	N/A	ENSP00000429430.1
TENM2	ENST00000520394.5	TSL:1	c.614-16_614-15insTTT	intron	N/A	ENSP00000427874.1
TENM2	ENST00000519204.5	TSL:5	c.947-16_947-15insTTT	intron	N/A	ENSP00000428964.1

Frequencies

GnomAD3 genomes

AF:

0.0000884

AC:

AN:

147066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000227

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00117

AC:

202

AN:

172048

AF XY:

0.00135

show subpopulations

Gnomad AFR exome

AF:

0.000460

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00191

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.000931

GnomAD4 exome

AF:

0.00100

AC:

1335

AN:

1332214

Hom.:

Cov.:

AF XY:

0.000921

AC XY:

610

AN XY:

662262

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000267

AC:

AN:

29980

American (AMR)

AF:

0.000474

AC:

AN:

37996

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

23962

East Asian (EAS)

AF:

0.00

AC:

AN:

36130

South Asian (SAS)

AF:

0.00161

AC:

124

AN:

77110

European-Finnish (FIN)

AF:

0.000670

AC:

AN:

47756

Middle Eastern (MID)

AF:

0.00179

AC:

AN:

3908

European-Non Finnish (NFE)

AF:

0.00105

AC:

1074

AN:

1020192

Other (OTH)

AF:

0.000707

AC:

AN:

55180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.266

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000884

AC:

AN:

147116

Hom.:

Cov.:

AF XY:

0.0000841

AC XY:

AN XY:

71372

show subpopulations

African (AFR)

AF:

0.0000497

AC:

AN:

40208

American (AMR)

AF:

0.00

AC:

AN:

14796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4672

European-Finnish (FIN)

AF:

0.000227

AC:

AN:

8804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000135

AC:

AN:

66882

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00276

Hom.:

100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-168062044-CTTT-CTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over