chr12-123688008-A-T

Variant names:

• chr12-123688008-A-T
• rs7298831
• NM_024809.5:c.765-43A>T

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.238

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=-0.82).
• 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
TCTN2	NM_024809.5	c.765-43A>T		intron_variant	Intron 6 of 17	ENST00000303372.7	NP_079085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7	c.765-43A>T		intron_variant	Intron 6 of 17	1	NM_024809.5	ENSP00000304941.5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62812 AN: 151834 Hom.: 13855 Cov.: 31

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

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

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

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

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

Other links and lift over

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