rs12831081

Positions:

• chr12-123695192-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024809.5(TCTN2):​c.1235-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,474,422 control chromosomes in the GnomAD database, including 102,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10273 hom., cov: 32)
  • Exomes 𝑓: 0.37 (92571 hom.)
• Consequence: TCTN2 NM_024809.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.58

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-123695192-A-G is Benign according to our data. Variant chr12-123695192-A-G is described in ClinVar as [Benign]. Clinvar id is 126284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN2	NM_024809.5	c.1235-28A>G		intron_variant		ENST00000303372.7	NP_079085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7	c.1235-28A>G		intron_variant		1	NM_024809.5	ENSP00000304941	P4

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54508 AN: 151896 Hom.: 10266 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.318 AC: 79285 AN: 249592 Hom.: 13955 AF XY: 0.325 AC XY: 43983 AN XY: 135436

Gnomad AFR exome AF: 0.418

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.0554

Gnomad SAS exome AF: 0.328

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.366 AC: 483773 AN: 1322406 Hom.: 92571 Cov.: 20 AF XY: 0.365 AC XY: 243076 AN XY: 665794

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.0471

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.359 AC: 54548 AN: 152016 Hom.: 10273 Cov.: 32 AF XY: 0.353 AC XY: 26257 AN XY: 74304

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.347

Alfa AF: 0.370 Hom.: 1931

Bravo AF: 0.359

Asia WGS AF: 0.184 AC: 644 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0090
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs12831081; hg19: chr12-124179739;