16-69356799-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005652.5(TERF2):c.*98_*99insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,028,340 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (29 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.263

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-69356799-C-CA is Benign according to our data. Variant chr16-69356799-C-CA is described in ClinVar as [Benign]. Clinvar id is 1265218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF2	NM_005652.5	c.*98_*99insT		3_prime_UTR_variant	10/10	ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.*98_*99insT		3_prime_UTR_variant	10/10	1	NM_005652.5	P1
TERF2	ENST00000566051.1	c.*177_*178insT		3_prime_UTR_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 2365 AN: 64526 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.00824

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00357

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0415

GnomAD4 exome AF: 0.141 AC: 136241 AN: 963812 Hom.: 5 Cov.: 0 AF XY: 0.140 AC XY: 66978 AN XY: 478800

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.0366 AC: 2361 AN: 64528 Hom.: 29 Cov.: 32 AF XY: 0.0358 AC XY: 1089 AN XY: 30426

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00360

Gnomad4 SAS AF: 0.0312

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0402

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs372147187; hg19: chr16-69390702;