Variant 16-1494301-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016111.4(TELO2):c.20A>G(p.Glu7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,612,066 control chromosomes in the GnomAD database, including 55,204 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.25 ( 4968 hom., cov: 31)

Exomes 𝑓: 0.26 ( 50236 hom. )

Consequence

TELO2
NM_016111.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0710

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3699194E-5).

BP6

Variant 16-1494301-A-G is Benign according to our data. Variant chr16-1494301-A-G is described in ClinVar as [Benign]. Clinvar id is 1245043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TELO2	NM_016111.4 linkuse as main transcript	c.20A>G	p.Glu7Gly	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.20A>G	p.Glu7Gly	missense_variant	2/21	1	NM_016111.4	ENSP00000262319	P1
TELO2	ENST00000497339.6 linkuse as main transcript	c.20A>G	p.Glu7Gly	missense_variant, NMD_transcript_variant	2/12	5		ENSP00000456383

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37473

AN:

151414

Hom.:

4954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.248

AC:

62265

AN:

250596

Hom.:

8642

AF XY:

0.248

AC XY:

33674

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.506

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.255

AC:

372998

AN:

1460536

Hom.:

50236

Cov.:

AF XY:

0.255

AC XY:

184906

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.248

AC:

37518

AN:

151530

Hom.:

4968

Cov.:

AF XY:

0.246

AC XY:

18236

AN XY:

74012

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.251

Hom.:

5425

Bravo

AF:

0.243

TwinsUK

AF:

0.265

AC:

984

ALSPAC

AF:

0.252

AC:

973

ESP6500AA

AF:

0.0150

AC:

ESP6500EA

AF:

0.0131

AC:

113

ExAC

AF:

0.252

AC:

30542

Asia WGS

AF:

0.388

AC:

1350

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.257

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Jan 24, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.099

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.074

MetaRNN

Benign

0.000034

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

REVEL

Benign

0.045

Sift

Benign

0.37

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.027

MPC

0.14

ClinPred

0.0061

GERP RS

-7.1

Varity_R

0.026

gMVP

0.13

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