12-123687063-G-T

Position:

• chr12-123687063-G-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.764+28G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,613,726 control chromosomes in the GnomAD database, including 408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (189 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (219 hom.)
• Consequence: TCTN2 NM_024809.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74

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=-0.92).
• BP6: Variant 12-123687063-G-T is Benign according to our data. Variant chr12-123687063-G-T is described in ClinVar as [Benign]. Clinvar id is 1271600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN2	NM_024809.5	c.764+28G>T		intron_variant		ENST00000303372.7	NP_079085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7	c.764+28G>T		intron_variant		1	NM_024809.5	ENSP00000304941.5

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4678 AN: 152150 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0129 AC: 3247 AN: 251324 Hom.: 99 AF XY: 0.0103 AC XY: 1397 AN XY: 135844

Gnomad AFR exome AF: 0.0862

Gnomad AMR exome AF: 0.0427

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.00696

Gnomad SAS exome AF: 0.00317

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.00436 AC: 6379 AN: 1461458 Hom.: 219 Cov.: 32 AF XY: 0.00396 AC XY: 2878 AN XY: 727040

Gnomad4 AFR exome AF: 0.0889

Gnomad4 AMR exome AF: 0.0453

Gnomad4 ASJ exome AF: 0.00719

Gnomad4 EAS exome AF: 0.00438

Gnomad4 SAS exome AF: 0.00334

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.00914

GnomAD4 genome AF: 0.0308 AC: 4686 AN: 152268 Hom.: 189 Cov.: 32 AF XY: 0.0309 AC XY: 2299 AN XY: 74450

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00273 Hom.: 0

Bravo AF: 0.0383

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs73418148; hg19: chr12-124171610;