chr12-123688008-A-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.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

2

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]

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 rank MANE Protein UniProt
TCTN2NM_024809.5 linkc.765-43A>T intron_variant Intron 6 of 17 ENST00000303372.7 NP_079085.2 Q96GX1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCTN2ENST00000303372.7 linkc.765-43A>T intron_variant Intron 6 of 17 1 NM_024809.5 ENSP00000304941.5 Q96GX1-1

Frequencies

GnomAD3 genomes
AF:
0.414
AC:
62812
AN:
151834
Hom.:
13855
Cov.:
31
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.:
32
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.:
31
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
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
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. -

not provided Benign:2
Jun 14, 2018
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. -

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

- -

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.

Other links and lift over

dbSNP: rs7298831; hg19: chr12-124172555; COSMIC: COSV57634615; API