16-69356799-CAAAAAAA-CAAAAAAAAA

Variant names:

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

Variant summary

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

The NM_005652.5(TERF2):​c.*97_*98dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,035,236 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 0.000031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (0 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: 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_*98dupTT		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_*98dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*97_*98dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*97_*98dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.0000308 AC: 2 AN: 64856 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: 0.000313

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000317

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00506 AC: 4914 AN: 970376 Hom.: 0 Cov.: 0 AF XY: 0.00506 AC XY: 2439 AN XY: 482196

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

African (AFR) AF: 0.00558 AC: 116 AN: 20778

American (AMR) AF: 0.00398 AC: 77 AN: 19326

Ashkenazi Jewish (ASJ) AF: 0.00426 AC: 64 AN: 15028

East Asian (EAS) AF: 0.00380 AC: 113 AN: 29754

South Asian (SAS) AF: 0.00418 AC: 218 AN: 52112

European-Finnish (FIN) AF: 0.00383 AC: 113 AN: 29474

Middle Eastern (MID) AF: 0.00382 AC: 12 AN: 3138

European-Non Finnish (NFE) AF: 0.00524 AC: 3985 AN: 760242

Other (OTH) AF: 0.00533 AC: 216 AN: 40524

⚠️ 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: 0.0000308 AC: 2 AN: 64860 Hom.: 0 Cov.: 32 AF XY: 0.0000327 AC XY: 1 AN XY: 30580

⚠️ 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: 17206

American (AMR) AF: 0.00 AC: 0 AN: 5528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1708

East Asian (EAS) AF: 0.00 AC: 0 AN: 2236

South Asian (SAS) AF: 0.00 AC: 0 AN: 2086

European-Finnish (FIN) AF: 0.000313 AC: 1 AN: 3200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.0000317 AC: 1 AN: 31586

Other (OTH) AF: 0.00 AC: 0 AN: 846

⚠️ 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.

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

Splicing

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

Other links and lift over

dbSNP: rs372147187; hg19: chr16-69390702;