16-69368349-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.947+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,608,744 control chromosomes in the GnomAD database, including 22,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1558 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21264 hom.)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.583

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=-0.81).
• BP6: Variant 16-69368349-C-T is Benign according to our data. Variant chr16-69368349-C-T is described in ClinVar as [Benign]. Clinvar id is 1262487.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF2	NM_005652.5	c.947+27G>A		intron_variant		ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.947+27G>A		intron_variant		1	NM_005652.5	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19558 AN: 151992 Hom.: 1559 Cov.: 32

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.131 AC: 32731 AN: 250158 Hom.: 2630 AF XY: 0.136 AC XY: 18353 AN XY: 135200

Gnomad AFR exome AF: 0.0590

Gnomad AMR exome AF: 0.0765

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.00136

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.164 AC: 239502 AN: 1456634 Hom.: 21264 Cov.: 29 AF XY: 0.164 AC XY: 119192 AN XY: 724864

Gnomad4 AFR exome AF: 0.0617

Gnomad4 AMR exome AF: 0.0830

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.000681

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.129 AC: 19552 AN: 152110 Hom.: 1558 Cov.: 32 AF XY: 0.127 AC XY: 9411 AN XY: 74364

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.155

Alfa AF: 0.150 Hom.: 389

Bravo AF: 0.123

Asia WGS AF: 0.0660 AC: 233 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 14, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.8
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs35439397; hg19: chr16-69402252;