16-69356756-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.187

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 -14 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_single_submitter, 1 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/exons	MANE	UniProt
TERF2	NM_005652.5	c.*142G>A		3_prime_UTR_variant	10/10	ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.*142G>A		3_prime_UTR_variant	10/10	1	NM_005652.5	P1
TERF2	ENST00000566051.1	c.*221G>A		3_prime_UTR_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3701 AN: 150568 Hom.: 158 Cov.: 31

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.: 71 Cov.: 10 AF XY: 0.00227 AC XY: 877 AN XY: 385562

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.: 31 AF XY: 0.0240 AC XY: 1766 AN XY: 73474

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.: 14

Bravo AF: 0.0280

Asia WGS AF: 0.00433 AC: 15 AN: 3478

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

Jun 27, 2019

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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

Other links and lift over

dbSNP: rs9922727; hg19: chr16-69390659;