Variant 12-123687063-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024809.5(TCTN2):c.764+28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,613,730 control chromosomes in the GnomAD database, including 420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 59 hom., cov: 32)

Exomes 𝑓: 0.019 ( 361 hom. )

Consequence

TCTN2
NM_024809.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.74

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-123687063-G-C is Benign according to our data. Variant chr12-123687063-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 261791.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 = 0.0239 (3635/152278) while in subpopulation AFR AF= 0.0469 (1948/41546). AF 95% confidence interval is 0.0452. There are 59 homozygotes in gnomad4. There are 1724 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN2	NM_024809.5 linkuse as main transcript	c.764+28G>C		intron_variant		ENST00000303372.7	NP_079085.2	Q96GX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7 linkuse as main transcript	c.764+28G>C		intron_variant		1	NM_024809.5	ENSP00000304941.5		Q96GX1-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3626

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.00660

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0176

AC:

4412

AN:

251324

Hom.:

AF XY:

0.0185

AC XY:

2513

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0477

Gnomad AMR exome

AF:

0.00728

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0375

Gnomad FIN exome

AF:

0.00813

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0187

AC:

27267

AN:

1461452

Hom.:

361

Cov.:

AF XY:

0.0192

AC XY:

13965

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.00859

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0392

Gnomad4 FIN exome

AF:

0.00863

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0239

AC:

3635

AN:

152278

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1724

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0469

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.00660

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00799

Hom.:

Bravo

AF:

0.0260

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.052

DANN

Benign

0.46

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