rs62177807

Variant names:

• chr2-165873877-T-C
• rs62177807
• NM_024753.5:c.*878A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024753.5(TTC21B):​c.*878A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,138 control chromosomes in the GnomAD database, including 1,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1063 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC21B NM_024753.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.376
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nephronophthisis 12

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• asphyxiating thoracic dystrophy 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-165873877-T-C is Benign according to our data. Variant chr2-165873877-T-C is described in ClinVar as Benign. ClinVar VariationId is 331801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	NM_024753.5	MANE Select	c.*878A>G		3_prime_UTR	Exon 29 of 29	NP_079029.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	ENST00000243344.8	TSL:1 MANE Select	c.*878A>G		3_prime_UTR	Exon 29 of 29	ENSP00000243344.7	Q7Z4L5-1
	TTC21B	ENST00000959804.1		c.*878A>G		3_prime_UTR	Exon 28 of 28	ENSP00000629863.1
	TTC21B	ENST00000679799.1		c.3806-2857A>G		intron	N/A	ENSP00000505208.1	A0A494C0N4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16935 AN: 152020 Hom.: 1065 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.111 AC: 16933 AN: 152138 Hom.: 1063 Cov.: 32 AF XY: 0.113 AC XY: 8419 AN XY: 74380

African (AFR) AF: 0.0599 AC: 2487 AN: 41522

American (AMR) AF: 0.0872 AC: 1332 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3468

East Asian (EAS) AF: 0.130 AC: 674 AN: 5184

South Asian (SAS) AF: 0.122 AC: 588 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1612 AN: 10552

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9121 AN: 67982

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.120 Hom.: 154

Bravo AF: 0.105

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Asphyxiating thoracic dystrophy 4 (1)
-	-	1	Nephronophthisis 12 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.56
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62177807; hg19: chr2-166730387;