Variant 12-123695192-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024809.5(TCTN2):c.1235-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,474,422 control chromosomes in the GnomAD database, including 102,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10273 hom., cov: 32)

Exomes 𝑓: 0.37 ( 92571 hom. )

Consequence

TCTN2
NM_024809.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.58

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-123695192-A-G is Benign according to our data. Variant chr12-123695192-A-G is described in ClinVar as [Benign]. Clinvar id is 126284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN2	NM_024809.5 linkuse as main transcript	c.1235-28A>G		intron_variant		ENST00000303372.7	NP_079085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7 linkuse as main transcript	c.1235-28A>G		intron_variant		1	NM_024809.5	ENSP00000304941	P4	Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54508

AN:

151896

Hom.:

10266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.0564

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.318

AC:

79285

AN:

249592

Hom.:

13955

AF XY:

0.325

AC XY:

43983

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.0554

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.366

AC:

483773

AN:

1322406

Hom.:

92571

Cov.:

AF XY:

0.365

AC XY:

243076

AN XY:

665794

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.0471

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.353

GnomAD4 genome

AF:

0.359

AC:

54548

AN:

152016

Hom.:

10273

Cov.:

AF XY:

0.353

AC XY:

26257

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.0563

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.370

Hom.:

1931

Bravo

AF:

0.359

Asia WGS

AF:

0.184

AC:

644

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0090

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over