rs7313032

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024809.5(TCTN2):c.891+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,599,370 control chromosomes in the GnomAD database, including 129,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14090 hom., cov: 30)

Exomes 𝑓: 0.39 ( 115840 hom. )

Consequence

TCTN2
NM_024809.5 splice_region, intron

Scores

Splicing: ADA: 0.00003429

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.407

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-123688184-G-A is Benign according to our data. Variant chr12-123688184-G-A is described in ClinVar as Benign. ClinVar VariationId is 126294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN2	NM_024809.5 link	c.891+7G>A		splice_region_variant, intron_variant	Intron 7 of 17	ENST00000303372.7	NP_079085.2	Q96GX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7 link	c.891+7G>A		splice_region_variant, intron_variant	Intron 7 of 17	1	NM_024809.5	ENSP00000304941.5		Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63125

AN:

151072

Hom.:

14072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.0632

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.416

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.398

GnomAD2 exomes

AF:

0.348

AC:

86940

AN:

250082

AF XY:

0.353

show subpopulations

Gnomad AFR exome

AF:

0.561

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.0619

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.390

AC:

565482

AN:

1448188

Hom.:

115840

Cov.:

AF XY:

0.390

AC XY:

281002

AN XY:

720850

show subpopulations

African (AFR)

AF:

0.571

AC:

18749

AN:

32864

American (AMR)

AF:

0.255

AC:

11374

AN:

44518

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8874

AN:

25956

East Asian (EAS)

AF:

0.0514

AC:

2030

AN:

39482

South Asian (SAS)

AF:

0.374

AC:

32078

AN:

85656

European-Finnish (FIN)

AF:

0.311

AC:

16460

AN:

52900

Middle Eastern (MID)

AF:

0.399

AC:

2277

AN:

5700

European-Non Finnish (NFE)

AF:

0.409

AC:

450707

AN:

1101256

Other (OTH)

AF:

0.383

AC:

22933

AN:

59856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

16739

33477

50216

66954

83693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13682

27364

41046

54728

68410

<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:

0.418

AC:

63181

AN:

151182

Hom.:

14090

Cov.:

AF XY:

0.412

AC XY:

30411

AN XY:

73790

show subpopulations

African (AFR)

AF:

0.559

AC:

23046

AN:

41204

American (AMR)

AF:

0.345

AC:

5238

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1208

AN:

3464

East Asian (EAS)

AF:

0.0632

AC:

326

AN:

5156

South Asian (SAS)

AF:

0.347

AC:

1656

AN:

4778

European-Finnish (FIN)

AF:

0.306

AC:

3159

AN:

10318

Middle Eastern (MID)

AF:

0.413

AC:

119

AN:

288

European-Non Finnish (NFE)

AF:

0.400

AC:

27143

AN:

67788

Other (OTH)

AF:

0.393

AC:

826

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1794

3587

5381

7174

8968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.412

Hom.:

7019

Bravo

AF:

0.424

Asia WGS

AF:

0.218

AC:

761

AN:

3478

EpiCase

AF:

0.405

EpiControl

AF:

0.403

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -

Jan 11, 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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel syndrome, type 8

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 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. -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome 24

Benign:1

Jan 13, 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

-0.79

CADD

Benign

0.30

(source)

DANN

Benign

0.81

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.0

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

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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