Variant rs78086946 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001102401.4(TTI2):c.834+11T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,613,760 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 45 hom., cov: 30)

Exomes 𝑓: 0.0013 ( 39 hom. )

Consequence

TTI2
NM_001102401.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

TTI2 (HGNC:26262): (TELO2 interacting protein 2) This gene encodes a regulator of the DNA damage response. The protein is a component of the Triple T complex (TTT) which also includes telomere length regulation protein and TELO2 interacting protein 1. The TTT complex is involved in cellular resistance to DNA damage stresses and may act as a regulator of phosphoinositide-3-kinase-related protein kinase (PIKK) abundance. [provided by RefSeq, May 2013]

TTI2 links:

TTI2 (HGNC:):

TTI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-33509735-A-C is Benign according to our data. Variant chr8-33509735-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 446028.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1839/152274) while in subpopulation AFR AF= 0.0421 (1748/41554). AF 95% confidence interval is 0.0404. There are 45 homozygotes in gnomad4. There are 872 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTI2	NM_001102401.4 linkuse as main transcript	c.834+11T>G		intron_variant		ENST00000431156.7	NP_001095871.1	Q6NXR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTI2	ENST00000431156.7 linkuse as main transcript	c.834+11T>G		intron_variant		1	NM_001102401.4	ENSP00000411169.3		Q6NXR4

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1839

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00329

AC:

828

AN:

251456

Hom.:

AF XY:

0.00219

AC XY:

298

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00129

AC:

1883

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

772

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0449

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.0121

AC:

1839

AN:

152274

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

872

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0421

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00591

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over