2-165951253-G-A

Position:

• chr2-165951253-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024753.5(TTC21B):​c.22-1529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 152,240 control chromosomes in the GnomAD database, including 122 homozygotes. 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: 𝑓 0.018 (122 hom., cov: 32)
• Consequence: TTC21B NM_024753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21B	NM_024753.5	c.22-1529C>T		intron_variant		ENST00000243344.8	NP_079029.3
TTC21B	XM_017004967.2	c.22-1529C>T		intron_variant			XP_016860456.1
TTC21B	XM_006712761.2	c.22-1529C>T		intron_variant			XP_006712824.1
TTC21B	XM_011511872.3	c.22-1529C>T		intron_variant			XP_011510174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8	c.22-1529C>T		intron_variant		1	NM_024753.5	ENSP00000243344.7

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2794 AN: 152122 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00670

Gnomad OTH AF: 0.0158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0183 AC: 2793 AN: 152240 Hom.: 122 Cov.: 32 AF XY: 0.0204 AC XY: 1520 AN XY: 74436

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.00670

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00921 Hom.: 11

Bravo AF: 0.0243

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.55

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: rs10497274; hg19: chr2-166807763;