12-123671503-C-T

Position:

chr12-123671503-C-T

Variant summary

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

The NM_024809.5(TCTN2):c.83-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,613,974 control chromosomes in the GnomAD database, including 1,194 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 0.055 ( 449 hom., cov: 32)

Exomes 𝑓: 0.023 ( 745 hom. )

Consequence

TCTN2
NM_024809.5 splice_region, intron

Scores

Splicing: ADA: 0.00004354

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.106

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=-0.63).

BP6

Variant 12-123671503-C-T is Benign according to our data. Variant chr12-123671503-C-T is described in ClinVar as [Benign]. Clinvar id is 126291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123671503-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TCTN2	NM_024809.5 linkuse as main transcript	c.83-4C>T	splice_region_variant, intron_variant	ENST00000303372.7	NP_079085.2	Q96GX1-1
TCTN2	NM_001143850.3 linkuse as main transcript	c.83-4C>T	splice_region_variant, intron_variant		NP_001137322.1	Q96GX1-2
TCTN2	NM_001410989.1 linkuse as main transcript	c.83-4C>T	splice_region_variant, intron_variant		NP_001397918.1
TCTN2	XM_017019974.2 linkuse as main transcript	c.83-4C>T	splice_region_variant, intron_variant		XP_016875463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7 linkuse as main transcript	c.83-4C>T		splice_region_variant, intron_variant		1	NM_024809.5	ENSP00000304941.5		Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.0546

AC:

8311

AN:

152130

Hom.:

451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.0344

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0305

AC:

7661

AN:

251372

Hom.:

250

AF XY:

0.0288

AC XY:

3914

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0500

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.00701

Gnomad SAS exome

AF:

0.0406

Gnomad FIN exome

AF:

0.00809

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0230

AC:

33637

AN:

1461726

Hom.:

745

Cov.:

AF XY:

0.0232

AC XY:

16838

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0540

Gnomad4 ASJ exome

AF:

0.0230

Gnomad4 EAS exome

AF:

0.00443

Gnomad4 SAS exome

AF:

0.0425

Gnomad4 FIN exome

AF:

0.00861

Gnomad4 NFE exome

AF:

0.0179

Gnomad4 OTH exome

AF:

0.0279

GnomAD4 genome

AF:

0.0547

AC:

8327

AN:

152248

Hom.:

449

Cov.:

AF XY:

0.0540

AC XY:

4022

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0748

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.00675

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0310

Hom.:

107

Bravo

AF:

0.0616

Asia WGS

AF:

0.0310

AC:

111

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0174

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	-	- -
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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.030

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