Genetic Variant TERF2:c.*94_*98delTTTTT (chr16-69356799-CAAAAA-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.*94_*98delTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000888 in 980,272 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Failed GnomAD Quality Control

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.94_98delTTTTT		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.94_98delTTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
TERF2	ENST00000903039.1		c.94_98delTTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
TERF2	ENST00000966429.1		c.94_98delTTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

64884

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

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:

0.0000888

AC:

AN:

980272

Hom.:

AF XY:

0.0000842

AC XY:

AN XY:

486954

show subpopulations

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

African (AFR)

AF:

0.000143

AC:

AN:

21012

American (AMR)

AF:

0.000154

AC:

AN:

19452

Ashkenazi Jewish (ASJ)

AF:

0.0000658

AC:

AN:

15194

East Asian (EAS)

AF:

0.000133

AC:

AN:

30024

South Asian (SAS)

AF:

0.000133

AC:

AN:

52504

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

29688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3166

European-Non Finnish (NFE)

AF:

0.0000781

AC:

AN:

768254

Other (OTH)

AF:

0.000146

AC:

AN:

40978

⚠️ 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: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

64884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30578

African (AFR)

AF:

0.00

AC:

AN:

17176

American (AMR)

AF:

0.00

AC:

AN:

5520

Ashkenazi Jewish (ASJ)

AF:

0.00

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:

3200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

31606

Other (OTH)

AF:

0.00

AC:

AN:

844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-69356799-CAAAAAAA-CAA

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