rs7298440

Variant names:

• chr12-123696502-C-T
• rs7298440
• NM_024809.5:c.1393+7C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-123696502-C-T
• chr12-123696502-C-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.1393+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,610,082 control chromosomes in the GnomAD database, including 113,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10303 hom., cov: 32)
  • Exomes 𝑓: 0.37 (102748 hom.)
• Consequence: TCTN2 NM_024809.5 splice_region, intron
• Scores: Splicing: ADA: 0.0008338
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.105
• Publications: 16 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=-0.8).
• BP6: Variant 12-123696502-C-T is Benign according to our data. Variant chr12-123696502-C-T is described in ClinVar as Benign. ClinVar VariationId is 126285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 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.1393+7C>T		splice_region intron	N/A	NP_079085.2
	TCTN2	NM_001143850.3		c.1390+7C>T		splice_region intron	N/A	NP_001137322.1	Q96GX1-2
	TCTN2	NM_001410989.1		c.1258+7C>T		splice_region intron	N/A	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.1393+7C>T		splice_region intron	N/A	ENSP00000304941.5	Q96GX1-1
	TCTN2	ENST00000426174.6	TSL:2	c.1390+7C>T		splice_region intron	N/A	ENSP00000395171.2	Q96GX1-2
	TCTN2	ENST00000965363.1		c.1315+7C>T		splice_region intron	N/A	ENSP00000635422.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54595 AN: 151928 Hom.: 10296 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.318 AC: 79926 AN: 251408 AF XY: 0.325

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.0554

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.368 AC: 536063 AN: 1458036 Hom.: 102748 Cov.: 31 AF XY: 0.367 AC XY: 266139 AN XY: 725540

African (AFR) AF: 0.423 AC: 14136 AN: 33388

American (AMR) AF: 0.202 AC: 9050 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 8277 AN: 26096

East Asian (EAS) AF: 0.0470 AC: 1865 AN: 39674

South Asian (SAS) AF: 0.333 AC: 28721 AN: 86160

European-Finnish (FIN) AF: 0.303 AC: 16162 AN: 53372

Middle Eastern (MID) AF: 0.366 AC: 2112 AN: 5766

European-Non Finnish (NFE) AF: 0.392 AC: 434430 AN: 1108602

Other (OTH) AF: 0.354 AC: 21310 AN: 60266

GnomAD4 genome AF: 0.359 AC: 54635 AN: 152046 Hom.: 10303 Cov.: 32 AF XY: 0.354 AC XY: 26314 AN XY: 74320

African (AFR) AF: 0.412 AC: 17096 AN: 41458

American (AMR) AF: 0.270 AC: 4118 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3468

East Asian (EAS) AF: 0.0562 AC: 291 AN: 5176

South Asian (SAS) AF: 0.311 AC: 1498 AN: 4816

European-Finnish (FIN) AF: 0.297 AC: 3136 AN: 10570

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.383 AC: 26064 AN: 67980

Other (OTH) AF: 0.347 AC: 732 AN: 2110

Alfa AF: 0.344 Hom.: 3215

Bravo AF: 0.359

Asia WGS AF: 0.185 AC: 646 AN: 3478

EpiCase AF: 0.387

EpiControl AF: 0.386

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Meckel syndrome, type 8 (3)
-	-	1	Joubert syndrome 24 (1)
-	-	1	Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00083
dbscSNV1_RF	Benign	0.080
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: rs7298440; hg19: chr12-124181049; COSMIC: COSV57632846;