16-69356799-CAAAAAAA-CAAAAA

Variant names:

• chr16-69356799-CAA-C
• rs372147187
• NM_005652.5:c.*97_*98delTT

Variant summary

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

The NM_005652.5(TERF2):​c.*97_*98delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 996,510 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.033 (0 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• 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: 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.*97_*98delTT		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.*97_*98delTT		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*97_*98delTT		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*97_*98delTT		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.000448 AC: 29 AN: 64784 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000363

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000443

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000317

Gnomad OTH AF: 0.00119

GnomAD4 exome AF: 0.0330 AC: 30728 AN: 931726 Hom.: 0 AF XY: 0.0336 AC XY: 15521 AN XY: 462354

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

African (AFR) AF: 0.0329 AC: 659 AN: 20042

American (AMR) AF: 0.0449 AC: 829 AN: 18468

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 566 AN: 14452

East Asian (EAS) AF: 0.0378 AC: 1071 AN: 28340

South Asian (SAS) AF: 0.0514 AC: 2541 AN: 49430

European-Finnish (FIN) AF: 0.0378 AC: 1059 AN: 28050

Middle Eastern (MID) AF: 0.0326 AC: 99 AN: 3040

European-Non Finnish (NFE) AF: 0.0308 AC: 22486 AN: 731078

Other (OTH) AF: 0.0365 AC: 1418 AN: 38826

⚠️ 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: 0.000448 AC: 29 AN: 64784 Hom.: 0 Cov.: 32 AF XY: 0.000557 AC XY: 17 AN XY: 30528

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

African (AFR) AF: 0.000175 AC: 3 AN: 17170

American (AMR) AF: 0.000363 AC: 2 AN: 5510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1712

East Asian (EAS) AF: 0.000443 AC: 1 AN: 2256

South Asian (SAS) AF: 0.00 AC: 0 AN: 2100

European-Finnish (FIN) AF: 0.00378 AC: 12 AN: 3178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.000317 AC: 10 AN: 31548

Other (OTH) AF: 0.00119 AC: 1 AN: 842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000333067), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53
Mutation Taster		=99/1	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;