chr2-165953686-T-TCACCC

Variant names:

• chr2-165953686-T-TCACCC
• NM_024753.5:c.19_20insGGGTG

Variant summary

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

The NM_024753.5(TTC21B):​c.19_20insGGGTG​(p.Lys7ArgfsTer5) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 557,028 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: 26)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: TTC21B NM_024753.5 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

Genes affected

TTC21B (HGNC:25660): (tetratricopeptide repeat domain 21B) This gene encodes a member of TTC21 family, containing several tetratricopeptide repeat (TPR) domains. This protein is localized to the cilium axoneme, and may play a role in retrograde intraflagellar transport in cilia. Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [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 19 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
TTC21B	NM_024753.5	c.19_20insGGGTG	p.Lys7ArgfsTer5	frameshift_variant, splice_region_variant	Exon 1 of 29	ENST00000243344.8	NP_079029.3
TTC21B	XM_017004967.2	c.19_20insGGGTG	p.Lys7ArgfsTer5	frameshift_variant, splice_region_variant	Exon 1 of 28		XP_016860456.1
TTC21B	XM_006712761.2	c.19_20insGGGTG	p.Lys7ArgfsTer5	frameshift_variant, splice_region_variant	Exon 1 of 23		XP_006712824.1
TTC21B	XM_011511872.3	c.19_20insGGGTG	p.Lys7ArgfsTer5	frameshift_variant, splice_region_variant	Exon 1 of 21		XP_011510174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8	c.19_20insGGGTG	p.Lys7ArgfsTer5	frameshift_variant, splice_region_variant	Exon 1 of 29	1	NM_024753.5	ENSP00000243344.7

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000898 AC: 5 AN: 557028 Hom.: 0 Cov.: 36 AF XY: 0.0000107 AC XY: 3 AN XY: 279136

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: 0.0000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

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: chr2-166810196;