NM_005652.5:c.*98dupT

Variant names:

• chr16-69356799-C-CA
• rs372147187
• NM_005652.5:c.*98dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005652.5(TERF2):​c.*98dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,028,340 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (29 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.263
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 16-69356799-C-CA is Benign according to our data. Variant chr16-69356799-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1265218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0366 (2361/64528) while in subpopulation AFR AF = 0.0517 (884/17112). AF 95% confidence interval is 0.0488. There are 29 homozygotes in GnomAd4. There are 1089 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2361 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005652.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	NM_005652.5	MANE Select	c.*98dupT		3_prime_UTR	Exon 10 of 10	NP_005643.2	Q15554-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	ENST00000254942.8	TSL:1 MANE Select	c.*98dupT		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*98dupT		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*98dupT		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 2365 AN: 64526 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.00824

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00357

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0415

GnomAD4 exome AF: 0.141 AC: 136241 AN: 963812 Hom.: 5 Cov.: 0 AF XY: 0.140 AC XY: 66978 AN XY: 478800

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.144 AC: 2983 AN: 20698

American (AMR) AF: 0.100 AC: 1929 AN: 19256

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 2002 AN: 14936

East Asian (EAS) AF: 0.122 AC: 3593 AN: 29540

South Asian (SAS) AF: 0.110 AC: 5733 AN: 51930

European-Finnish (FIN) AF: 0.116 AC: 3404 AN: 29272

Middle Eastern (MID) AF: 0.132 AC: 411 AN: 3118

European-Non Finnish (NFE) AF: 0.147 AC: 110606 AN: 754778

Other (OTH) AF: 0.139 AC: 5580 AN: 40284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0366 AC: 2361 AN: 64528 Hom.: 29 Cov.: 32 AF XY: 0.0358 AC XY: 1089 AN XY: 30426

African (AFR) AF: 0.0517 AC: 884 AN: 17112

American (AMR) AF: 0.0305 AC: 168 AN: 5502

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 29 AN: 1704

East Asian (EAS) AF: 0.00360 AC: 8 AN: 2222

South Asian (SAS) AF: 0.0312 AC: 65 AN: 2082

European-Finnish (FIN) AF: 0.0238 AC: 76 AN: 3190

Middle Eastern (MID) AF: 0.0500 AC: 5 AN: 100

European-Non Finnish (NFE) AF: 0.0347 AC: 1089 AN: 31406

Other (OTH) AF: 0.0402 AC: 34 AN: 846

Alfa AF: 0.00218 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs372147187; hg19: chr16-69390702; COSMIC: COSV105039665; COSMIC: COSV105039665;