rs7313032

Variant names:

• chr12-123688184-G-A
• rs7313032
• NM_024809.5:c.891+7G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-123688184-G-A
• chr12-123688184-G-C
• chr12-123688184-G-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.891+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,599,370 control chromosomes in the GnomAD database, including 129,930 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 0.42 (14090 hom., cov: 30)
  • Exomes 𝑓: 0.39 (115840 hom.)
• Consequence: TCTN2 NM_024809.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003429
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.407
• Publications: 20 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=-0.79).
• BP6: Variant 12-123688184-G-A is Benign according to our data. Variant chr12-123688184-G-A is described in ClinVar as Benign. ClinVar VariationId is 126294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 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.891+7G>A		splice_region intron	N/A	NP_079085.2
	TCTN2	NM_001143850.3		c.888+7G>A		splice_region intron	N/A	NP_001137322.1
	TCTN2	NM_001410989.1		c.891+7G>A		splice_region intron	N/A	NP_001397918.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN2	ENST00000303372.7	TSL:1 MANE Select	c.891+7G>A		splice_region intron	N/A	ENSP00000304941.5
	TCTN2	ENST00000426174.6	TSL:2	c.888+7G>A		splice_region intron	N/A	ENSP00000395171.2
	TCTN2	ENST00000965363.1		c.891+7G>A		splice_region intron	N/A	ENSP00000635422.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63125 AN: 151072 Hom.: 14072 Cov.: 30

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.416

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.348 AC: 86940 AN: 250082 AF XY: 0.353

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.0619

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.390 AC: 565482 AN: 1448188 Hom.: 115840 Cov.: 37 AF XY: 0.390 AC XY: 281002 AN XY: 720850

African (AFR) AF: 0.571 AC: 18749 AN: 32864

American (AMR) AF: 0.255 AC: 11374 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8874 AN: 25956

East Asian (EAS) AF: 0.0514 AC: 2030 AN: 39482

South Asian (SAS) AF: 0.374 AC: 32078 AN: 85656

European-Finnish (FIN) AF: 0.311 AC: 16460 AN: 52900

Middle Eastern (MID) AF: 0.399 AC: 2277 AN: 5700

European-Non Finnish (NFE) AF: 0.409 AC: 450707 AN: 1101256

Other (OTH) AF: 0.383 AC: 22933 AN: 59856

GnomAD4 genome AF: 0.418 AC: 63181 AN: 151182 Hom.: 14090 Cov.: 30 AF XY: 0.412 AC XY: 30411 AN XY: 73790

African (AFR) AF: 0.559 AC: 23046 AN: 41204

American (AMR) AF: 0.345 AC: 5238 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1208 AN: 3464

East Asian (EAS) AF: 0.0632 AC: 326 AN: 5156

South Asian (SAS) AF: 0.347 AC: 1656 AN: 4778

European-Finnish (FIN) AF: 0.306 AC: 3159 AN: 10318

Middle Eastern (MID) AF: 0.413 AC: 119 AN: 288

European-Non Finnish (NFE) AF: 0.400 AC: 27143 AN: 67788

Other (OTH) AF: 0.393 AC: 826 AN: 2102

Alfa AF: 0.412 Hom.: 7019

Bravo AF: 0.424

Asia WGS AF: 0.218 AC: 761 AN: 3478

EpiCase AF: 0.405

EpiControl AF: 0.403

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Meckel syndrome, type 8 (3)
-	-	3	not specified (3)
-	-	1	Joubert syndrome 24 (1)
-	-	1	Meckel-Gruber syndrome;C0431399:Joubert syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.30
DANN	Benign	0.81
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0
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: rs7313032; hg19: chr12-124172731;