16-69366972-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005652.5(TERF2):​c.1175T>C​(p.Leu392Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TERF2
NM_005652.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31
Variant links:
Genes affected
TERF2 (HGNC:11729): (telomeric repeat binding factor 2) This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21052971).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TERF2NM_005652.5 linkc.1175T>C p.Leu392Pro missense_variant Exon 7 of 10 ENST00000254942.8 NP_005643.2 Q15554-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TERF2ENST00000254942.8 linkc.1175T>C p.Leu392Pro missense_variant Exon 7 of 10 1 NM_005652.5 ENSP00000254942.3 Q15554-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251326
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1049T>C (p.L350P) alteration is located in exon 7 (coding exon 7) of the TERF2 gene. This alteration results from a T to C substitution at nucleotide position 1049, causing the leucine (L) at amino acid position 350 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.6
.;N
REVEL
Benign
0.16
Sift
Uncertain
0.014
.;D
Sift4G
Uncertain
0.014
D;T
Vest4
0.12
MVP
0.53
ClinPred
0.80
D
GERP RS
5.0
Varity_R
0.094
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1236772828; hg19: chr16-69400875; API