rs73418153

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024809.5(TCTN2):c.873A>G(p.Ala291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,610,976 control chromosomes in the GnomAD database, including 1,189 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: 0.022 ( 739 hom. )

Consequence

TCTN2
NM_024809.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.58

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 -21 ACMG points.

BP4

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

BP6

Variant 12-123688159-A-G is Benign according to our data. Variant chr12-123688159-A-G is described in ClinVar as [Benign]. Clinvar id is 126292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123688159-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN2	NM_024809.5 linkuse as main transcript	c.873A>G	p.Ala291=	synonymous_variant	7/18	ENST00000303372.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN2	ENST00000303372.7 linkuse as main transcript	c.873A>G	p.Ala291=	synonymous_variant	7/18	1	NM_024809.5	P4	Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8313

AN:

151964

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0747

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00693

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.00663

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0297

AC:

7469

AN:

251070

Hom.:

250

AF XY:

0.0280

AC XY:

3800

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0492

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.00696

Gnomad SAS exome

AF:

0.0385

Gnomad FIN exome

AF:

0.00809

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0222

AC:

32434

AN:

1458902

Hom.:

739

Cov.:

AF XY:

0.0224

AC XY:

16262

AN XY:

725838

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.0532

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.00439

Gnomad4 SAS exome

AF:

0.0414

Gnomad4 FIN exome

AF:

0.00862

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0276

GnomAD4 genome

AF:

0.0548

AC:

8330

AN:

152074

Hom.:

450

Cov.:

AF XY:

0.0541

AC XY:

4025

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0746

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00695

Gnomad4 SAS

AF:

0.0345

Gnomad4 FIN

AF:

0.00663

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0312

Hom.:

105

Bravo

AF:

0.0616

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 04, 2016	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. -
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. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Joubert syndrome 24

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.020

Dann

Benign

0.55

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

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