16-69356799-CAAAAAAA-CAAAA

Variant names:

• chr16-69356799-CAAA-C
• rs372147187
• NM_005652.5:c.*96_*98delTTT

Variant summary

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

The NM_005652.5(TERF2):​c.*96_*98delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,028,178 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 0.000077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (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.*96_*98delTTT		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.*96_*98delTTT		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*96_*98delTTT		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*96_*98delTTT		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.0000771 AC: 5 AN: 64842 Hom.: 0 Cov.: 32

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: 0.000314

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000127

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00634 AC: 6106 AN: 963336 Hom.: 0 AF XY: 0.00640 AC XY: 3063 AN XY: 478502

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

African (AFR) AF: 0.00561 AC: 116 AN: 20662

American (AMR) AF: 0.00872 AC: 166 AN: 19038

Ashkenazi Jewish (ASJ) AF: 0.00732 AC: 109 AN: 14884

East Asian (EAS) AF: 0.00699 AC: 206 AN: 29454

South Asian (SAS) AF: 0.0100 AC: 514 AN: 51210

European-Finnish (FIN) AF: 0.00757 AC: 220 AN: 29066

Middle Eastern (MID) AF: 0.00645 AC: 20 AN: 3102

European-Non Finnish (NFE) AF: 0.00595 AC: 4494 AN: 755706

Other (OTH) AF: 0.00649 AC: 261 AN: 40214

⚠️ 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: 0.0000771 AC: 5 AN: 64842 Hom.: 0 Cov.: 32 AF XY: 0.000131 AC XY: 4 AN XY: 30560

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

African (AFR) AF: 0.00 AC: 0 AN: 17172

American (AMR) AF: 0.00 AC: 0 AN: 5518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1714

East Asian (EAS) AF: 0.00 AC: 0 AN: 2256

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

European-Finnish (FIN) AF: 0.000314 AC: 1 AN: 3188

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

European-Non Finnish (NFE) AF: 0.000127 AC: 4 AN: 31584

Other (OTH) AF: 0.00 AC: 0 AN: 842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53

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;