16-69361309-G-A

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454

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=-0.85).
• 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_single_submitter, 1 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/exons	MANE	UniProt
TERF2	NM_005652.5	c.1426+95C>T		intron_variant		ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.1426+95C>T		intron_variant		1	NM_005652.5	P1
TERF2	ENST00000566051.1	c.68+95C>T		intron_variant		3
TERF2	ENST00000567130.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6974 AN: 151662 Hom.: 213 Cov.: 31

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.: 9 AF XY: 0.0593 AC XY: 22529 AN XY: 379878

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.: 31 AF XY: 0.0449 AC XY: 3329 AN XY: 74178

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.: 34

Bravo AF: 0.0469

Asia WGS AF: 0.0550 AC: 192 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 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	10
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

Other links and lift over

dbSNP: rs34295116; hg19: chr16-69395212;