12-123672090-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024809.5(TCTN2):c.225C>T(p.Asn75Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,613,876 control chromosomes in the GnomAD database, including 1,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 450 hom., cov: 32)

Exomes 𝑓: 0.023 ( 745 hom. )

Consequence

TCTN2
NM_024809.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.841

Publications

10 publications found

Variant links:

Genes affected

TCTN2 (HGNC:25774): (tectonic family member 2) This gene encodes a type I membrane protein that belongs to the tectonic family. Studies in mice suggest that this protein may be involved in hedgehog signaling, and essential for ciliogenesis. Mutations in this gene are associated with Meckel syndrome type 8. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

TCTN2 Gene-Disease associations (from GenCC):

Joubert syndrome 24
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TCTN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-123672090-C-T is Benign according to our data. Variant chr12-123672090-C-T is described in ClinVar as Benign. ClinVar VariationId is 126287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.841 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TCTN2	NM_024809.5 link	c.225C>T	p.Asn75Asn	synonymous_variant	Exon 3 of 18	ENST00000303372.7	NP_079085.2
TCTN2	NM_001143850.3 link	c.225C>T	p.Asn75Asn	synonymous_variant	Exon 3 of 18		NP_001137322.1
TCTN2	NM_001410989.1 link	c.225C>T	p.Asn75Asn	synonymous_variant	Exon 3 of 17		NP_001397918.1
TCTN2	XM_017019974.2 link	c.225C>T	p.Asn75Asn	synonymous_variant	Exon 3 of 17		XP_016875463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7 link	c.225C>T	p.Asn75Asn	synonymous_variant	Exon 3 of 18	1	NM_024809.5	ENSP00000304941.5

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8313

AN:

152090

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0748

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00694

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0305

AC:

7671

AN:

251492

AF XY:

0.0288

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0500

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.00701

Gnomad FIN exome

AF:

0.00813

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.0230

AC:

33578

AN:

1461668

Hom.:

745

Cov.:

AF XY:

0.0231

AC XY:

16826

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.136

AC:

4551

AN:

33456

American (AMR)

AF:

0.0540

AC:

2413

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0229

AC:

599

AN:

26132

East Asian (EAS)

AF:

0.00443

AC:

176

AN:

39696

South Asian (SAS)

AF:

0.0425

AC:

3666

AN:

86242

European-Finnish (FIN)

AF:

0.00863

AC:

461

AN:

53416

Middle Eastern (MID)

AF:

0.0323

AC:

186

AN:

5766

European-Non Finnish (NFE)

AF:

0.0178

AC:

19827

AN:

1111850

Other (OTH)

AF:

0.0281

AC:

1699

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

1832

3663

5495

7326

9158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.0547

AC:

8330

AN:

152208

Hom.:

450

Cov.:

AF XY:

0.0540

AC XY:

4021

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.134

AC:

5578

AN:

41494

American (AMR)

AF:

0.0747

AC:

1142

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3466

East Asian (EAS)

AF:

0.00695

AC:

AN:

5178

South Asian (SAS)

AF:

0.0348

AC:

168

AN:

4828

European-Finnish (FIN)

AF:

0.00669

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0171

AC:

1162

AN:

68020

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

380

760

1140

1520

1900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0331

Hom.:

106

Bravo

AF:

0.0616

Asia WGS

AF:

0.0310

AC:

111

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0174

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 04, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joubert syndrome 24

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Meckel syndrome, type 8

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Meckel-Gruber syndrome;C0431399:Joubert syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.78

PhyloP100

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over