Genetic Variant TERF2:c.1426+95C>T (chr16-69361309-G-A) – 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.1426+95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 870,292 control chromosomes in the GnomAD database, including 1,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 219 hom., cov: 31)

Exomes 𝑓: 0.058 ( 1454 hom. )

Consequence

TERF2
NM_005652.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.454

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=-0.85).

BP6

Variant 16-69361309-G-A is Benign according to our data. Variant chr16-69361309-G-A is described in ClinVar as [Benign]. Clinvar id is 1180317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF2	NM_005652.5 link	c.1426+95C>T		intron_variant	Intron 8 of 9	ENST00000254942.8	NP_005643.2	Q15554-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TERF2	ENST00000254942.8 link	c.1426+95C>T	intron_variant	Intron 8 of 9	1	NM_005652.5	ENSP00000254942.3	Q15554-3
TERF2	ENST00000566051.1 link	c.67+95C>T	intron_variant	Intron 1 of 1	3		ENSP00000463079.1	J3KTN8
TERF2	ENST00000567130.1 link	n.*43C>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

6974

AN:

151662

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.0597

Gnomad ASJ

AF:

0.0502

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0831

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0609

Gnomad OTH

AF:

0.0466

GnomAD4 exome

AF:

0.0583

AC:

41897

AN:

718518

Hom.:

1454

Cov.:

AF XY:

0.0593

AC XY:

22529

AN XY:

379878

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.0519

Gnomad4 ASJ exome

AF:

0.0495

Gnomad4 EAS exome

AF:

0.0215

Gnomad4 SAS exome

AF:

0.0787

Gnomad4 FIN exome

AF:

0.0352

Gnomad4 NFE exome

AF:

0.0638

Gnomad4 OTH exome

AF:

0.0562

GnomAD4 genome

AF:

0.0461

AC:

6995

AN:

151774

Hom.:

219

Cov.:

AF XY:

0.0449

AC XY:

3329

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.0598

Gnomad4 ASJ

AF:

0.0502

Gnomad4 EAS

AF:

0.0193

Gnomad4 SAS

AF:

0.0840

Gnomad4 FIN

AF:

0.0333

Gnomad4 NFE

AF:

0.0609

Gnomad4 OTH

AF:

0.0533

Alfa

AF:

0.0491

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.0550

AC:

192

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

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.76

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