12-123688199-T-C

Variant names:

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+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,590,942 control chromosomes in the GnomAD database, including 168,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20487 hom., cov: 30)

Exomes 𝑓: 0.44 ( 147714 hom. )

Consequence

TCTN2
NM_024809.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.561

Publications

11 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=-0.82).

BP6

Variant 12-123688199-T-C is Benign according to our data. Variant chr12-123688199-T-C is described in ClinVar as [Benign]. Clinvar id is 126293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN2	NM_024809.5 link	c.891+22T>C		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+22T>C		intron_variant	Intron 7 of 17	1	NM_024809.5	ENSP00000304941.5		Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75254

AN:

151266

Hom.:

20442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.550

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.464

GnomAD2 exomes

AF:

0.412

AC:

102436

AN:

248338

AF XY:

0.418

show subpopulations

Gnomad AFR exome

AF:

0.729

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.357

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.442

AC:

636453

AN:

1439566

Hom.:

147714

Cov.:

AF XY:

0.443

AC XY:

317895

AN XY:

717106

show subpopulations

African (AFR)

AF:

0.735

AC:

24058

AN:

32712

American (AMR)

AF:

0.279

AC:

12367

AN:

44330

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

9988

AN:

25854

East Asian (EAS)

AF:

0.120

AC:

4760

AN:

39544

South Asian (SAS)

AF:

0.491

AC:

41830

AN:

85276

European-Finnish (FIN)

AF:

0.354

AC:

18533

AN:

52334

Middle Eastern (MID)

AF:

0.440

AC:

2504

AN:

5694

European-Non Finnish (NFE)

AF:

0.453

AC:

496151

AN:

1094326

Other (OTH)

AF:

0.441

AC:

26262

AN:

59496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

15587

31175

46762

62350

77937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14690

29380

44070

58760

73450

<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:

0.498

AC:

75347

AN:

151376

Hom.:

20487

Cov.:

AF XY:

0.490

AC XY:

36260

AN XY:

73938

show subpopulations

African (AFR)

AF:

0.721

AC:

29678

AN:

41158

American (AMR)

AF:

0.381

AC:

5807

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1367

AN:

3464

East Asian (EAS)

AF:

0.148

AC:

763

AN:

5158

South Asian (SAS)

AF:

0.462

AC:

2223

AN:

4808

European-Finnish (FIN)

AF:

0.346

AC:

3609

AN:

10438

Middle Eastern (MID)

AF:

0.472

AC:

137

AN:

290

European-Non Finnish (NFE)

AF:

0.446

AC:

30288

AN:

67836

Other (OTH)

AF:

0.467

AC:

980

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1735

3471

5206

6942

8677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.399

Hom.:

1993

Bravo

AF:

0.506

Asia WGS

AF:

0.347

AC:

1210

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

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

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel syndrome, type 8

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

-0.82

CADD

Benign

0.17

(source)

DANN

Benign

0.40

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(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

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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