16-1497457-CG-TC

Variant names:

• chr16-1497457-CG-TC
• NM_016111.4:c.779_780delCGinsTC
• TELO2 p.Pro260Leu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PS1_Moderate

The NM_016111.4(TELO2):​c.779_780delCGinsTC​(p.Pro260Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P260P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TELO2 NM_016111.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21
• Publications: 0 publications found

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: Orphanet, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PS1: Transcript NM_016111.4 (TELO2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TELO2	NM_016111.4	MANE Select	c.779_780delCGinsTC	p.Pro260Leu	missense	N/A	NP_057195.2	Q9Y4R8
	TELO2	NM_001351846.2		c.779_780delCGinsTC	p.Pro260Leu	missense	N/A	NP_001338775.1	Q9Y4R8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TELO2	ENST00000262319.11	TSL:1 MANE Select	c.779_780delCGinsTC	p.Pro260Leu	missense	N/A	ENSP00000262319.6	Q9Y4R8
	TELO2	ENST00000889741.1		c.779_780delCGinsTC	p.Pro260Leu	missense	N/A	ENSP00000559800.1
	TELO2	ENST00000914530.1		c.779_780delCGinsTC	p.Pro260Leu	missense	N/A	ENSP00000584589.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-1547458;