16-69356799-CAAAAAAA-CAAAAAA

Variant names:

• chr16-69356799-CA-C
• rs372147187
• NM_005652.5:c.*98delT

Variant summary

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

The NM_005652.5(TERF2):​c.*98delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
  • Failed GnomAD Quality Control
• 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.*98delT		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.*98delT		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*98delT		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*98delT		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 176 AN: 64848 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000641

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00272

Gnomad ASJ AF: 0.00234

Gnomad EAS AF: 0.000443

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00831

GnomAD4 exome AF: 0.214 AC: 202106 AN: 944392 Hom.: 1 Cov.: 0 AF XY: 0.216 AC XY: 101139 AN XY: 468594

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

African (AFR) AF: 0.215 AC: 4362 AN: 20282

American (AMR) AF: 0.241 AC: 4530 AN: 18792

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 3302 AN: 14592

East Asian (EAS) AF: 0.238 AC: 6810 AN: 28578

South Asian (SAS) AF: 0.233 AC: 11758 AN: 50464

European-Finnish (FIN) AF: 0.232 AC: 6568 AN: 28262

Middle Eastern (MID) AF: 0.202 AC: 616 AN: 3042

European-Non Finnish (NFE) AF: 0.210 AC: 155656 AN: 740952

Other (OTH) AF: 0.216 AC: 8504 AN: 39428

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00274 AC: 178 AN: 64852 Hom.: 0 Cov.: 32 AF XY: 0.00285 AC XY: 87 AN XY: 30566

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

African (AFR) AF: 0.000639 AC: 11 AN: 17210

American (AMR) AF: 0.00272 AC: 15 AN: 5522

Ashkenazi Jewish (ASJ) AF: 0.00234 AC: 4 AN: 1712

East Asian (EAS) AF: 0.000447 AC: 1 AN: 2236

South Asian (SAS) AF: 0.00240 AC: 5 AN: 2086

European-Finnish (FIN) AF: 0.0163 AC: 52 AN: 3200

Middle Eastern (MID) AF: 0.0100 AC: 1 AN: 100

European-Non Finnish (NFE) AF: 0.00257 AC: 81 AN: 31578

Other (OTH) AF: 0.00948 AC: 8 AN: 844

⚠️ 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: 0.000223 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

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; COSMIC: COSV107293208; COSMIC: COSV107293208;