16-69357811-C-G

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.1427-250G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 150,920 control chromosomes in the GnomAD database, including 7,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7472 hom., cov: 31)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0800

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 16-69357811-C-G is Benign according to our data. Variant chr16-69357811-C-G is described in ClinVar as [Benign]. Clinvar id is 1228279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF2	NM_005652.5	c.1427-250G>C		intron_variant		ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.1427-250G>C		intron_variant		1	NM_005652.5	P1
TERF2	ENST00000566051.1	c.69-755G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45158 AN: 150814 Hom.: 7438 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.300 AC: 45250 AN: 150920 Hom.: 7472 Cov.: 31 AF XY: 0.296 AC XY: 21832 AN XY: 73660

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.304

Alfa AF: 0.128 Hom.: 195

Bravo AF: 0.305

Asia WGS AF: 0.285 AC: 992 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	-0.88
Cadd	Benign	7.1
Dann	Benign	0.50

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: rs9925619; hg19: chr16-69391714;