16-69356678-T-C

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.*220A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 438,718 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (141 hom., cov: 32)
  • Exomes 𝑓: 0.049 (401 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147

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=-0.88).
• BP6: Variant 16-69356678-T-C is Benign according to our data. Variant chr16-69356678-T-C is described in ClinVar as [Benign]. Clinvar id is 1228096.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF2	NM_005652.5	c.*220A>G		3_prime_UTR_variant	10/10	ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.*220A>G		3_prime_UTR_variant	10/10	1	NM_005652.5	P1
TERF2	ENST00000566051.1	c.*299A>G		3_prime_UTR_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5539 AN: 151684 Hom.: 141 Cov.: 32

Gnomad AFR AF: 0.00930

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.0488 AC: 14005 AN: 286920 Hom.: 401 Cov.: 5 AF XY: 0.0499 AC XY: 7520 AN XY: 150652

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0173

Gnomad4 ASJ exome AF: 0.0568

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0614

Gnomad4 FIN exome AF: 0.0431

Gnomad4 NFE exome AF: 0.0562

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0365 AC: 5537 AN: 151798 Hom.: 141 Cov.: 32 AF XY: 0.0363 AC XY: 2692 AN XY: 74140

Gnomad4 AFR AF: 0.00928

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0559

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0465 Hom.: 24

Bravo AF: 0.0336

Asia WGS AF: 0.0170 AC: 60 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	-0.88
Cadd	Benign	6.4
Dann	Benign	0.53

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: rs56106543; hg19: chr16-69390581;