Variant rs7298831 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.765-43A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,608,040 control chromosomes in the GnomAD database, including 129,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13872 hom., cov: 31)

Exomes 𝑓: 0.39 ( 115770 hom. )

Consequence

TCTN2
NM_024809.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.238

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=-0.82).

BP6

Variant 12-123688008-A-T is Benign according to our data. Variant chr12-123688008-A-T is described in ClinVar as [Benign]. Clinvar id is 126290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 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.765-43A>T		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.765-43A>T		intron_variant		1	NM_024809.5	ENSP00000304941	P4	Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62812

AN:

151834

Hom.:

13855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0626

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.391

GnomAD3 exomes

AF:

0.348

AC:

87439

AN:

251046

Hom.:

16807

AF XY:

0.353

AC XY:

47994

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.0624

Gnomad SAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.391

AC:

569068

AN:

1456090

Hom.:

115770

Cov.:

AF XY:

0.390

AC XY:

282606

AN XY:

724468

show subpopulations

Gnomad4 AFR exome

AF:

0.560

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.0515

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.414

AC:

62868

AN:

151950

Hom.:

13872

Cov.:

AF XY:

0.408

AC XY:

30274

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.547

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.0625

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.386

Alfa

AF:

0.402

Hom.:

2295

Bravo

AF:

0.420

Asia WGS

AF:

0.217

AC:

758

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

-0.82

CADD

Benign

0.76

DANN

Benign

0.74

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