dbSNP rs202020308: TELO2:p.Cys367Tyr (chr16-1500444-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

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

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

TELO2 links:

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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 ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016111.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TELO2	NM_016111.4	MANE Select	c.1100G>A	p.Cys367Tyr	missense	Exon 8 of 21	NP_057195.2
	TELO2	NM_001351846.2		c.1100G>A	p.Cys367Tyr	missense	Exon 8 of 21	NP_001338775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TELO2	ENST00000262319.11	TSL:1 MANE Select	c.1100G>A	p.Cys367Tyr	missense	Exon 8 of 21	ENSP00000262319.6
	TELO2	ENST00000497339.6	TSL:5	n.1100G>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000456383.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724868

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25944

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00

AC:

AN:

85662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111072

Other (OTH)

AF:

0.00

AC:

AN:

60162

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.7

PhyloP100

7.9

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.92

MutPred

0.64

Loss of catalytic residue at L368 (P = 0.0419)

MVP

0.67

MPC

0.72

ClinPred

0.99

GERP RS

5.0

Varity_R

0.77

gMVP

0.60

Mutation Taster

=58/42

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over