16-1494312-GC-AA

Variant names:

• chr16-1494312-GC-AA
• rs2142446269
• NM_016111.4:c.31_32delGCinsAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016111.4(TELO2):​c.31_32delGCinsAA​(p.Ala11Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TELO2 NM_016111.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.505

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TELO2	NM_016111.4	c.31_32delGCinsAA	p.Ala11Asn	missense_variant		ENST00000262319.11	NP_057195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TELO2	ENST00000262319.11	c.31_32delGCinsAA	p.Ala11Asn	missense_variant		1	NM_016111.4	ENSP00000262319.6
TELO2	ENST00000497339.6	n.31_32delGCinsAA		non_coding_transcript_exon_variant	Exon 2 of 12	5		ENSP00000456383.1

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

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Oct 18, 2018

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Uncertain:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 11 of the TELO2 protein (p.Ala11Asn). This variant is present in population databases (no rsID available, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with TELO2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1334826). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2142446269; hg19: chr16-1544313;