rs73418153

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024809.5(TCTN2):​c.873A>G​(p.Ala291Ala) 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

2

Clinical Significance

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

Conservation

PhyloP100: -3.58

Publications

7 publications found
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 Gene-Disease associations (from GenCC):
  • Joubert syndrome 24
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • Joubert syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Meckel syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.
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 rank MANE Protein UniProt
TCTN2NM_024809.5 linkc.873A>G p.Ala291Ala synonymous_variant Exon 7 of 18 ENST00000303372.7 NP_079085.2 Q96GX1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCTN2ENST00000303372.7 linkc.873A>G p.Ala291Ala synonymous_variant Exon 7 of 18 1 NM_024809.5 ENSP00000304941.5 Q96GX1-1

Frequencies

GnomAD3 genomes
AF:
0.0547
AC:
8313
AN:
151964
Hom.:
452
Cov.:
32
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
GnomAD2 exomes
AF:
0.0297
AC:
7469
AN:
251070
AF XY:
0.0280
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 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.:
35
AF XY:
0.0224
AC XY:
16262
AN XY:
725838
show subpopulations
African (AFR)
AF:
0.132
AC:
4378
AN:
33104
American (AMR)
AF:
0.0532
AC:
2374
AN:
44630
Ashkenazi Jewish (ASJ)
AF:
0.0226
AC:
589
AN:
26102
East Asian (EAS)
AF:
0.00439
AC:
174
AN:
39658
South Asian (SAS)
AF:
0.0414
AC:
3561
AN:
86038
European-Finnish (FIN)
AF:
0.00862
AC:
460
AN:
53356
Middle Eastern (MID)
AF:
0.0314
AC:
181
AN:
5758
European-Non Finnish (NFE)
AF:
0.0172
AC:
19056
AN:
1109968
Other (OTH)
AF:
0.0276
AC:
1661
AN:
60288
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.422
Heterozygous variant carriers
0
1482
2964
4445
5927
7409
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
840
1680
2520
3360
4200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0548
AC:
8330
AN:
152074
Hom.:
450
Cov.:
32
AF XY:
0.0541
AC XY:
4025
AN XY:
74338
show subpopulations
African (AFR)
AF:
0.135
AC:
5585
AN:
41472
American (AMR)
AF:
0.0746
AC:
1139
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.0225
AC:
78
AN:
3466
East Asian (EAS)
AF:
0.00695
AC:
36
AN:
5182
South Asian (SAS)
AF:
0.0345
AC:
166
AN:
4816
European-Finnish (FIN)
AF:
0.00663
AC:
70
AN:
10564
Middle Eastern (MID)
AF:
0.0308
AC:
9
AN:
292
European-Non Finnish (NFE)
AF:
0.0171
AC:
1163
AN:
67998
Other (OTH)
AF:
0.0398
AC:
84
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
370
741
1111
1482
1852
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
86
172
258
344
430
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0318
Hom.:
133
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:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Mar 04, 2016
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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. -

-
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

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. -

-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Joubert syndrome 24 Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Meckel-Gruber syndrome;C0431399:Joubert syndrome Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.020
DANN
Benign
0.55
PhyloP100
-3.6
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs73418153; hg19: chr12-124172706; API