16-69368349-C-T

Variant names:

• chr16-69368349-C-T
• rs35439397
• NM_005652.5:c.947+27G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.583
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1262487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TERF2	NM_005652.5	c.947+27G>A		intron_variant	Intron 6 of 9	ENST00000254942.8	NP_005643.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF2	ENST00000254942.8	c.947+27G>A		intron_variant	Intron 6 of 9	1	NM_005652.5	ENSP00000254942.3

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

GnomAD2 exomes AF: 0.131 AC: 32731 AN: 250158 AF XY: 0.136

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 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

African (AFR) AF: 0.0617 AC: 2059 AN: 33364

American (AMR) AF: 0.0830 AC: 3710 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 4696 AN: 26104

East Asian (EAS) AF: 0.000681 AC: 27 AN: 39662

South Asian (SAS) AF: 0.137 AC: 11831 AN: 86064

European-Finnish (FIN) AF: 0.133 AC: 7041 AN: 53094

Middle Eastern (MID) AF: 0.253 AC: 1141 AN: 4514

European-Non Finnish (NFE) AF: 0.180 AC: 199488 AN: 1109016

Other (OTH) AF: 0.158 AC: 9509 AN: 60142

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

African (AFR) AF: 0.0637 AC: 2642 AN: 41508

American (AMR) AF: 0.118 AC: 1805 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3470

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5164

South Asian (SAS) AF: 0.120 AC: 577 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1333 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12106 AN: 67978

Other (OTH) AF: 0.155 AC: 326 AN: 2110

Alfa AF: 0.147 Hom.: 390

Bravo AF: 0.123

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35439397; hg19: chr16-69402252;