NM_016111.4:c.1100G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_016111.4(TELO2):​c.1100G>A​(p.Cys367Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C367F) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TELO2
NM_016111.4 missense

Scores

6
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.94

Publications

0 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: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr16-1500444-G-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 236225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TELO2NM_016111.4 linkc.1100G>A p.Cys367Tyr missense_variant Exon 8 of 21 ENST00000262319.11 NP_057195.2 Q9Y4R8B4DXS2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TELO2ENST00000262319.11 linkc.1100G>A p.Cys367Tyr missense_variant Exon 8 of 21 1 NM_016111.4 ENSP00000262319.6 Q9Y4R8
TELO2ENST00000497339.6 linkn.1100G>A non_coding_transcript_exon_variant Exon 8 of 12 5 ENSP00000456383.1 H3BRS3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1457534
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724868
African (AFR)
AF:
0.00
AC:
0
AN:
33460
American (AMR)
AF:
0.00
AC:
0
AN:
44302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25944
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39538
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85662
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51710
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5684
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111072
Other (OTH)
AF:
0.00
AC:
0
AN:
60162
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.14
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.64
D
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.050
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.7
M
PhyloP100
7.9
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-5.1
D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.92
MutPred
0.64
Loss of catalytic residue at L368 (P = 0.0419);
MVP
0.67
MPC
0.72
ClinPred
0.99
D
GERP RS
5.0
Varity_R
0.77
gMVP
0.60
Mutation Taster
=58/42
polymorphism

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: rs202020308; hg19: chr16-1550445; API