12-123671161-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024809.5(TCTN2):c.-80G>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 0.00166 in 1,366,446 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (17 hom.)
• Consequence: TCTN2 NM_024809.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.128

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-123671161-G-A is Benign according to our data. Variant chr12-123671161-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1188149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00814 (1240/152340) while in subpopulation AFR AF= 0.0281 (1170/41590). AF 95% confidence interval is 0.0268. There are 13 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN2	NM_024809.5	c.-80G>A		5_prime_UTR_variant	1/18	ENST00000303372.7
TCTN2	NM_001143850.3	c.-80G>A		5_prime_UTR_variant	1/18
TCTN2	NM_001410989.1	c.-80G>A		5_prime_UTR_variant	1/17
TCTN2	XM_017019974.2	c.-80G>A		5_prime_UTR_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN2	ENST00000303372.7	c.-80G>A		5_prime_UTR_variant	1/18	1	NM_024809.5	P4

Frequencies

GnomAD3 genomes AF: 0.00812 AC: 1236 AN: 152222 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.000850 AC: 1032 AN: 1214106 Hom.: 17 Cov.: 17 AF XY: 0.000710 AC XY: 432 AN XY: 608686

Gnomad4 AFR exome AF: 0.0294

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000183

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000763

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00814 AC: 1240 AN: 152340 Hom.: 13 Cov.: 32 AF XY: 0.00742 AC XY: 553 AN XY: 74484

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00817 Hom.: 1

Bravo AF: 0.00948

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.9
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs191193522; hg19: chr12-124155708;