rs113301547

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024809.5(TCTN2):c.1585C>G(p.Leu529Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,614,114 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

TCTN2
NM_024809.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.931

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 (MetaRNN=0.0047388077).

BP6

Variant 12-123699783-C-G is Benign according to our data. Variant chr12-123699783-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 215940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00355 (540/152282) while in subpopulation AFR AF= 0.012 (498/41552). AF 95% confidence interval is 0.0111. There are 2 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN2	NM_024809.5 link	c.1585C>G	p.Leu529Val	missense_variant	Exon 14 of 18	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.1585C>G	p.Leu529Val	missense_variant	Exon 14 of 18	1	NM_024809.5	ENSP00000304941.5		Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.000959

AC:

241

AN:

251378

Hom.:

AF XY:

0.000788

AC XY:

107

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000423

AC:

619

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

288

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00355

AC:

540

AN:

152282

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000463

Hom.:

Bravo

AF:

0.00369

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00122

AC:

148

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 13, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 15, 2022

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.8

.;M

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.25

Sift

Benign

0.096

T;T

Sift4G

Uncertain

0.048

D;D

Polyphen

0.36

.;B

Vest4

0.15

MVP

0.57

MPC

0.20

ClinPred

0.038

GERP RS

5.0

Varity_R

0.15

gMVP

0.53

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