dbSNP rs74464871: TENM2:p.Asp2003Glu (chr5-168246948-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395460.1(TENM2):c.6009C>A(p.Asp2003Glu) 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 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D2003D) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TENM2
NM_001395460.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.814

Publications

0 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:

TENM2-AS1 (HGNC:56066): (TENM2 antisense RNA 2)

TENM2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18287432).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TENM2	NM_001395460.1	MANE Select	c.6009C>A	p.Asp2003Glu	missense	Exon 29 of 31	NP_001382389.1	Q9NT68-1
TENM2	NM_001122679.2		c.5982C>A	p.Asp1994Glu	missense	Exon 28 of 30	NP_001116151.1
TENM2	NM_001368145.1		c.5532C>A	p.Asp1844Glu	missense	Exon 25 of 27	NP_001355074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENM2	ENST00000518659.6	TSL:5 MANE Select	c.6009C>A	p.Asp2003Glu	missense	Exon 29 of 31	ENSP00000429430.1	Q9NT68-1
TENM2	ENST00000520394.5	TSL:1	c.5292C>A	p.Asp1764Glu	missense	Exon 23 of 25	ENSP00000427874.1	F8VNQ3
TENM2	ENST00000519204.5	TSL:5	c.5646C>A	p.Asp1882Glu	missense	Exon 26 of 28	ENSP00000428964.1	G3V106

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111862

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

0.32

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.18

MetaSVM

Uncertain

0.054

MutationAssessor

Benign

1.2

PhyloP100

-0.81

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.66

Sift

Benign

0.29

Sift4G

Benign

0.36

Polyphen

0.42

Vest4

0.35

MutPred

0.43

Loss of sheet (P = 0.0457)

MVP

0.57

MPC

0.47

ClinPred

0.73

GERP RS

-2.7

Varity_R

0.39

gMVP

0.27

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over