Genetic Variant TERF2:c.*95_*98delTTTT (chr16-69356799-CAAAA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005652.5(TERF2):c.*95_*98delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,040,084 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

TERF2
NM_005652.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.534

Publications

0 publications found

Variant links:

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]

TERF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.95_98delTTTT		3_prime_UTR	Exon 10 of 10	NP_005643.2	Q15554-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TERF2	ENST00000254942.8	TSL:1 MANE Select	c.95_98delTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
TERF2	ENST00000903039.1		c.95_98delTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
TERF2	ENST00000966429.1		c.95_98delTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes

AF:

0.0000154

AC:

AN:

64876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000583

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00111

AC:

1081

AN:

975208

Hom.:

AF XY:

0.00116

AC XY:

560

AN XY:

484402

show subpopulations

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

African (AFR)

AF:

0.00110

AC:

AN:

20946

American (AMR)

AF:

0.00217

AC:

AN:

19340

Ashkenazi Jewish (ASJ)

AF:

0.00132

AC:

AN:

15108

East Asian (EAS)

AF:

0.00127

AC:

AN:

29822

South Asian (SAS)

AF:

0.00200

AC:

104

AN:

52106

European-Finnish (FIN)

AF:

0.00156

AC:

AN:

29480

Middle Eastern (MID)

AF:

0.00190

AC:

AN:

3158

European-Non Finnish (NFE)

AF:

0.00100

AC:

765

AN:

764456

Other (OTH)

AF:

0.000907

AC:

AN:

40792

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.245

Heterozygous variant carriers

159

317

476

634

793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000154

AC:

AN:

64876

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

30570

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17176

American (AMR)

AF:

0.00

AC:

AN:

5520

Ashkenazi Jewish (ASJ)

AF:

0.000583

AC:

AN:

1714

East Asian (EAS)

AF:

0.00

AC:

AN:

2256

South Asian (SAS)

AF:

0.00

AC:

AN:

2100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

31596

Other (OTH)

AF:

0.00

AC:

AN:

844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over