2-165940934-T-A

Position:

• chr2-165940934-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024753.5(TTC21B):​c.710+93A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,432,942 control chromosomes in the GnomAD database, including 17,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1592 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16323 hom.)
• Consequence: TTC21B NM_024753.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0750

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]

TTC21B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-165940934-T-A is Benign according to our data. Variant chr2-165940934-T-A is described in ClinVar as [Benign]. Clinvar id is 1281967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21B	NM_024753.5	c.710+93A>T		intron_variant		ENST00000243344.8	NP_079029.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8	c.710+93A>T		intron_variant		1	NM_024753.5	ENSP00000243344.7

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18502 AN: 151990 Hom.: 1592 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.146 AC: 186905 AN: 1280832 Hom.: 16323 AF XY: 0.144 AC XY: 92768 AN XY: 644532

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.0536

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.122 AC: 18513 AN: 152110 Hom.: 1592 Cov.: 32 AF XY: 0.129 AC XY: 9591 AN XY: 74362

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.108

Alfa AF: 0.119 Hom.: 156

Bravo AF: 0.121

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.53

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: rs12623658; hg19: chr2-166797444; COSMIC: COSV54634119;