rs144863771

Positions:

chr16-1494313-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_016111.4(TELO2):c.32C>A(p.Ala11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,398 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 12 hom. )

Consequence

TELO2
NM_016111.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.505

Variant links:

Genes affected

TELO2 (HGNC:29099): (telomere maintenance 2) This gene encodes a protein that functions as an S-phase checkpoint protein in the cell cycle. The protein may also play a role in DNA repair.[provided by RefSeq, Mar 2009]

TELO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067305863).

BP6

Variant 16-1494313-C-A is Benign according to our data. Variant chr16-1494313-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 376945.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000939 (143/152256) while in subpopulation NFE AF= 0.00113 (77/68022). AF 95% confidence interval is 0.000928. There are 0 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TELO2	NM_016111.4 linkuse as main transcript	c.32C>A	p.Ala11Asp	missense_variant	2/21	ENST00000262319.11	NP_057195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TELO2	ENST00000262319.11 linkuse as main transcript	c.32C>A	p.Ala11Asp	missense_variant	2/21	1	NM_016111.4	ENSP00000262319	P1
TELO2	ENST00000497339.6 linkuse as main transcript	c.32C>A	p.Ala11Asp	missense_variant, NMD_transcript_variant	2/12	5		ENSP00000456383

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00137

AC:

343

AN:

250980

Hom.:

AF XY:

0.00144

AC XY:

195

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00114

AC:

1670

AN:

1461142

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

852

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.000227

Gnomad4 NFE exome

AF:

0.000937

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152256

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00115

AC:

140

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00190

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 18, 2017	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.0

DANN

Benign

0.78

DEOGEN2

Benign

0.12

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.61

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

REVEL

Benign

0.012

Sift

Benign

0.030

Sift4G

Benign

0.081

Polyphen

0.026

Vest4

0.39

MVP

0.19

MPC

0.20

ClinPred

0.014

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.097

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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