Genetic Variant TERF2:c.*142G>A (chr16-69356756-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005652.5(TERF2):c.*142G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 915,902 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 158 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 71 hom. )

Consequence

TERF2
NM_005652.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.187

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]

TERF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-69356756-C-T is Benign according to our data. Variant chr16-69356756-C-T is described in ClinVar as [Benign]. Clinvar id is 1281238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF2	NM_005652.5 link	c.*142G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000254942.8	NP_005643.2	Q15554-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF2	ENST00000254942 link	c.*142G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_005652.5	ENSP00000254942.3		Q15554-3
TERF2	ENST00000566051.1 link	c.*221G>A		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000463079.1		J3KTN8

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3701

AN:

150568

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00901

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000575

Gnomad OTH

AF:

0.0198

GnomAD4 exome

AF:

0.00251

AC:

1921

AN:

765226

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

877

AN XY:

385562

show subpopulations

Gnomad4 AFR exome

AF:

0.0817

Gnomad4 AMR exome

AF:

0.00473

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000341

Gnomad4 SAS exome

AF:

0.000195

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000355

Gnomad4 OTH exome

AF:

0.00609

GnomAD4 genome

AF:

0.0246

AC:

3707

AN:

150676

Hom.:

158

Cov.:

AF XY:

0.0240

AC XY:

1766

AN XY:

73474

show subpopulations

Gnomad4 AFR

AF:

0.0853

Gnomad4 AMR

AF:

0.00899

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000575

Gnomad4 OTH

AF:

0.0196

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0280

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 27, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.9

DANN

Benign

0.87

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over