12-123671310-TG-TGGGGG

Variant names:

• chr12-123671310-T-TGGGG
• NM_024809.5:c.73_76dupGGGG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_024809.5(TCTN2):​c.73_76dupGGGG​(p.Asp26GlyfsTer53) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCTN2 NM_024809.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN2	NM_024809.5	c.73_76dupGGGG	p.Asp26GlyfsTer53	frameshift_variant	Exon 1 of 18	ENST00000303372.7	NP_079085.2
TCTN2	NM_001143850.3	c.73_76dupGGGG	p.Asp26GlyfsTer53	frameshift_variant	Exon 1 of 18		NP_001137322.1
TCTN2	NM_001410989.1	c.73_76dupGGGG	p.Asp26GlyfsTer53	frameshift_variant	Exon 1 of 17		NP_001397918.1
TCTN2	XM_017019974.2	c.73_76dupGGGG	p.Asp26GlyfsTer53	frameshift_variant	Exon 1 of 17		XP_016875463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7	c.73_76dupGGGG	p.Asp26GlyfsTer53	frameshift_variant	Exon 1 of 18	1	NM_024809.5	ENSP00000304941.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-124155857;