12-123687063-G-T

Variant names:

• chr12-123687063-G-T
• rs73418148
• NM_024809.5:c.764+28G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Joubert syndrome 24

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024809.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN2	NM_024809.5	MANE Select	c.764+28G>T		intron	N/A	NP_079085.2
	TCTN2	NM_001143850.3		c.761+28G>T		intron	N/A	NP_001137322.1
	TCTN2	NM_001410989.1		c.764+28G>T		intron	N/A	NP_001397918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN2	ENST00000303372.7	TSL:1 MANE Select	c.764+28G>T		intron	N/A	ENSP00000304941.5
	TCTN2	ENST00000426174.6	TSL:2	c.761+28G>T		intron	N/A	ENSP00000395171.2
	TCTN2	ENST00000679504.1		c.761+28G>T		intron	N/A	ENSP00000505006.1

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

GnomAD2 exomes AF: 0.0129 AC: 3247 AN: 251324 AF XY: 0.0103

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 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

African (AFR) AF: 0.0889 AC: 2976 AN: 33466

American (AMR) AF: 0.0453 AC: 2027 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00719 AC: 188 AN: 26134

East Asian (EAS) AF: 0.00438 AC: 174 AN: 39694

South Asian (SAS) AF: 0.00334 AC: 288 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5762

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1111656

Other (OTH) AF: 0.00914 AC: 552 AN: 60372

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

African (AFR) AF: 0.0873 AC: 3628 AN: 41536

American (AMR) AF: 0.0588 AC: 898 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5184

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68034

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.56
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73418148; hg19: chr12-124171610;