chr12-123671186-C-A

Variant names:

• chr12-123671186-C-A
• rs78846567
• NM_024809.5:c.-55C>A

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.-55C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,539,316 control chromosomes in the GnomAD database, including 2,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (134 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2000 hom.)
• Consequence: TCTN2 NM_024809.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.489
• Publications: 8 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, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• Meckel syndrome, type 8

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.73).
• BP6: Variant 12-123671186-C-A is Benign according to our data. Variant chr12-123671186-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 307542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0561 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN2	NM_024809.5	MANE Select	c.-55C>A		5_prime_UTR	Exon 1 of 18	NP_079085.2
	TCTN2	NM_001143850.3		c.-55C>A		5_prime_UTR	Exon 1 of 18	NP_001137322.1	Q96GX1-2
	TCTN2	NM_001410989.1		c.-55C>A		5_prime_UTR	Exon 1 of 17	NP_001397918.1	A0A7P0T8X4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN2	ENST00000303372.7	TSL:1 MANE Select	c.-55C>A		5_prime_UTR	Exon 1 of 18	ENSP00000304941.5	Q96GX1-1
	TCTN2	ENST00000426174.6	TSL:2	c.-55C>A		5_prime_UTR	Exon 1 of 18	ENSP00000395171.2	Q96GX1-2
	TCTN2	ENST00000965363.1		c.-55C>A		5_prime_UTR	Exon 1 of 17	ENSP00000635422.1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5693 AN: 152140 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.00871

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0459

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0512 AC: 71005 AN: 1387058 Hom.: 2000 Cov.: 23 AF XY: 0.0512 AC XY: 35373 AN XY: 690360

African (AFR) AF: 0.00731 AC: 233 AN: 31886

American (AMR) AF: 0.0224 AC: 884 AN: 39386

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 922 AN: 25384

East Asian (EAS) AF: 0.000106 AC: 4 AN: 37616

South Asian (SAS) AF: 0.0452 AC: 3695 AN: 81828

European-Finnish (FIN) AF: 0.0476 AC: 2195 AN: 46084

Middle Eastern (MID) AF: 0.0598 AC: 338 AN: 5656

European-Non Finnish (NFE) AF: 0.0564 AC: 59857 AN: 1061422

Other (OTH) AF: 0.0498 AC: 2877 AN: 57796

GnomAD4 genome AF: 0.0374 AC: 5693 AN: 152258 Hom.: 134 Cov.: 32 AF XY: 0.0370 AC XY: 2754 AN XY: 74444

African (AFR) AF: 0.00869 AC: 361 AN: 41564

American (AMR) AF: 0.0249 AC: 380 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4826

European-Finnish (FIN) AF: 0.0459 AC: 487 AN: 10620

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3916 AN: 68012

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0371 Hom.: 32

Bravo AF: 0.0334

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Joubert syndrome 24 (1)
-	-	1	Meckel syndrome, type 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.40
PhyloP100		0.49
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=110/190	disease causing

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: rs78846567; hg19: chr12-124155733; COSMIC: COSV57632274;