Genetic Variant TCTN2:c.-95G>T (chr12-123671146-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024809.5(TCTN2):c.-95G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000929 in 1,076,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

TCTN2
NM_024809.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.902

Publications

0 publications found

Variant links:

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

TCTN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCTN2	NM_024809.5	MANE Select	c.-95G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_079085.2
TCTN2	NM_024809.5	MANE Select	c.-95G>T	5_prime_UTR	Exon 1 of 18	NP_079085.2
TCTN2	NM_001143850.3		c.-95G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001137322.1	Q96GX1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCTN2	ENST00000303372.7	TSL:1 MANE Select	c.-95G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000304941.5	Q96GX1-1
TCTN2	ENST00000303372.7	TSL:1 MANE Select	c.-95G>T	5_prime_UTR	Exon 1 of 18	ENSP00000304941.5	Q96GX1-1
TCTN2	ENST00000426174.6	TSL:2	c.-95G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000395171.2	Q96GX1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.29e-7

AC:

AN:

1076678

Hom.:

Cov.:

AF XY:

0.00000184

AC XY:

AN XY:

544580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25424

American (AMR)

AF:

0.00

AC:

AN:

35364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23264

East Asian (EAS)

AF:

0.00

AC:

AN:

34452

South Asian (SAS)

AF:

0.00

AC:

AN:

73192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4932

European-Non Finnish (NFE)

AF:

0.00000126

AC:

AN:

794938

Other (OTH)

AF:

0.00

AC:

AN:

47484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.2

(source)

DANN

Benign

0.97

PhyloP100

0.90

PromoterAI

0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over