GeneBe

NM_016111.4:c.514C>T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_016111.4(TELO2):​c.514C>T​(p.Gln172*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000685 in 1,459,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TELO2
NM_016111.4 stop_gained

Scores

4
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.94

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • TELO2-related intellectual disability-neurodevelopmental disorder
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TELO2NM_016111.4 linkc.514C>T p.Gln172* stop_gained Exon 3 of 21 ENST00000262319.11 NP_057195.2 Q9Y4R8B4DXS2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TELO2ENST00000262319.11 linkc.514C>T p.Gln172* stop_gained Exon 3 of 21 1 NM_016111.4 ENSP00000262319.6 Q9Y4R8
TELO2ENST00000497339.6 linkn.514C>T non_coding_transcript_exon_variant Exon 3 of 12 5 ENSP00000456383.1 H3BRS3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459102
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
725958
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50772
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111938
Other (OTH)
AF:
0.00
AC:
0
AN:
60358
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
38
DANN
Uncertain
1.0
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.92
D
PhyloP100
3.9
Vest4
0.11
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=11/189
disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs878853272; hg19: chr16-1545525; API