TERTc.2097C>TBenign

Print report

Variant interpretation report

TERT c.2097C>T, p.(Ala699=)

NM_198253.2:c.2097C>T NP_937983.2:p.(Ala699=) View identifiers

Classification

Benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.

Benign.A benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About TERT

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 stand alone (benign) · 1 strong (benign) · 1 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 16 Benign
Pipeline record: 27 May 2026

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): Population frequency is above the benign stand-alone threshold of 1%. This variant is present at AF 1.11328% in gnomAD v2.1 and AF 1.28122% in gnomAD-Canada, with much higher East Asian frequencies of 8.10613% in gnomAD v2.1 and 5.10623% in gnomAD v4.1.
BS1 (strong): Population frequency is above the strong benign threshold of 0.3%. This variant is present at AF 1.11328% in gnomAD v2.1, AF 0.89897% in gnomAD v4.1, and AF 1.28122% in gnomAD-Canada.
BP7 (supporting): This is a synonymous variant, NP_937983.2:p.(Ala699=), and available splicing prediction does not support RNA disruption. SpliceAI shows a maximum delta score of 0.00, which is below a level suggesting splice impact.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 3

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3

BA1Stand alone

BA1 · stand alone

Population frequency is above the benign stand-alone threshold of 1%. This variant is present at AF 1.11328% in gnomAD v2.1 and AF 1.28122% in gnomAD-Canada, with much higher East Asian frequencies of 8.10613% in gnomAD v2.1 and 5.10623% in gnomAD v4.1.

BS1Strong

BS1 · strong

Population frequency is above the strong benign threshold of 0.3%. This variant is present at AF 1.11328% in gnomAD v2.1, AF 0.89897% in gnomAD v4.1, and AF 1.28122% in gnomAD-Canada.

BP7Supporting

BP7 · supporting

This is a synonymous variant, NP_937983.2:p.(Ala699=), and available splicing prediction does not support RNA disruption. SpliceAI shows a maximum delta score of 0.00, which is below a level suggesting splice impact.

Recorded classification: Benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BP7 supporting benign; combination = 1 stand-alone benign, which maps to Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

14,255 / 1,585,702 alleles

gnomAD v4.1: 14,255 / 1,585,702 alleles. Recorded AF 0.00898971. Recorded homozygote count 169.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.0111328; MAF= 1.11328%, 2562/230130 alleles, homozygotes = 78) and has highest observed frequency in the East Asian population (AF= 0.0810613; MAF= 8.10613%, 1332/16432 alleles, homozygotes = 68); grpmax FAF= 0.0770165.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0128122; MAF= 1.28122%, 236/18420 alleles, homozygotes = 5) and has highest observed frequency in the eas population (AF= 0.064275; grpmax FAF95= 0.0533145).

Applied · BA1, BS1 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP7 → SpliceAI ↗

ClinVar submissions

16 reported laboratory submissions

16 Benign.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

3 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV57230878, n = 3 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

28 criteria with recorded statuses: 3 met · 4 not met · 13 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

The TERT c.2097C>T (p.Ala699=) variant has been reported in ClinVar as benign.

This variant is common in population databases, with AF 1.11328% in gnomAD v2.1, AF 0.89897% in gnomAD v4.1, and AF 1.28122% in gnomAD-Canada; the highest observed East Asian frequencies are 8.10613% in gnomAD v2.1 and 5.10623% in gnomAD v4.1, which is above benign frequency thresholds.

As a synonymous change, available in silico splicing evidence does not support RNA disruption; SpliceAI predicts no significant splice impact with a maximum delta score of 0.00.

Met · 3

BA1 Stand alonePopulation frequency is above the benign stand-alone threshold of 1%. This variant is present at AF 1.11328% in gnomAD v2.1 and AF 1.28122% in gnomAD-Canada, with much higher East Asian frequencies of 8.10613% in gnomAD v2.1 and 5.10623% in gnomAD v4.1. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 total AF 1.11328%
gnomAD v4.1 East Asian AF 5.10623%
gnomAD-Canada total AF 1.28122%

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS1 StrongPopulation frequency is above the strong benign threshold of 0.3%. This variant is present at AF 1.11328% in gnomAD v2.1, AF 0.89897% in gnomAD v4.1, and AF 1.28122% in gnomAD-Canada. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 total AF
gnomAD v4.1 total AF
gnomAD-Canada total AF

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BP7 SupportingThis is a synonymous variant, NP_937983.2:p.(Ala699=), and available splicing prediction does not support RNA disruption. SpliceAI shows a maximum delta score of 0.00, which is below a level suggesting splice impact. Details ▾Hide ▴

Evidence considered

synonymous consequence
SpliceAI max delta score 0.00

Sources

spliceai ↗

Not met · 4 · evaluated, threshold not reached

PS4 Available evidence does not show enrichment of this variant in affected individuals over controls, and the variant is common in population databases, which argues against PS4. Details ▾Hide ▴

Evidence considered

ClinVar benign reporting
population frequency data

Still missing

Case-control or statistically enriched case series data would be needed.

Sources

clinvar ↗gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PM1 This variant is not located in a demonstrated mutational hotspot or other established critical functional region without benign variation. Details ▾Hide ▴

Evidence considered

Cancer Hotspots review showing no hotspot row

Sources

hotspots ↗

PM2 This variant is not absent from population databases; it is present at AF 1.11328% in gnomAD v2.1, AF 0.89897% in gnomAD v4.1, and AF 1.28122% in gnomAD-Canada, so PM2 is not met. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 frequency
gnomAD v4.1 frequency
gnomAD-Canada frequency

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact, with a maximum delta score of 0.00. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score 0.00

Sources

spliceai ↗

Not assessed · 13 · no assessment recorded

PS2 No confirmed de novo data were identified for this variant. Details ▾Hide ▴

Still missing

Parental testing or a documented de novo report would be needed.

PS3 No well-established functional study demonstrating a damaging effect for this specific variant was identified. Details ▾Hide ▴

Evidence considered

OncoKB review context without variant-specific functional evidence

Still missing

A validated variant-specific functional or RNA study would be needed.

Sources

oncokb ↗

PM3 No data were identified showing this variant in trans with a pathogenic variant for a recessive disease mechanism. Details ▾Hide ▴

Still missing

Phase information and recessive case data would be needed.

PM6 No assumed de novo evidence was identified for this variant. Details ▾Hide ▴

Still missing

A documented de novo occurrence without full parental confirmation would be needed.

PP1 No segregation data were identified for this variant. Details ▾Hide ▴

Still missing

Family segregation data would be needed.

PP4 No phenotype-specific evidence was identified linking this variant to a highly specific TERT-related clinical presentation in a way that supports PP4. Details ▾Hide ▴

Still missing

Detailed phenotype data and phenotype-gene specificity would be needed.

PP5 External database assertions alone were not used as independent pathogenic evidence for this criterion. Details ▾Hide ▴

Evidence considered

ClinVar submission summary

Still missing

Primary evidence rather than assertion-based support would be needed.

Sources

clinvar ↗

BS2 Although the variant is seen in many population samples, no disease-specific framework was identified establishing that observation in unaffected adults is sufficient for BS2 in TERT-related disease. Details ▾Hide ▴

Evidence considered

population homozygote counts

Still missing

Disease-specific penetrance and unaffected-observation standards would be needed.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 No well-established functional study demonstrating a benign effect for this specific variant was identified. Details ▾Hide ▴

Evidence considered

review of available curated literature context

Still missing

A validated variant-specific functional or RNA study showing no damaging effect would be needed.

Sources

oncokb ↗

BS4 No non-segregation data were identified for this variant. Details ▾Hide ▴

Still missing

Family non-segregation evidence would be needed.

BP2 No phase data were identified showing this variant in trans with a pathogenic variant for a dominant disorder or in cis for a recessive disorder. Details ▾Hide ▴

Still missing

Phase and co-occurrence data would be needed.

BP5 No alternate molecular explanation was identified that would make this variant an incidental finding relative to a fully explained phenotype. Details ▾Hide ▴

Still missing

Detailed phenotype and alternate-cause data would be needed.

BP6 External benign assertions were not used as independent evidence for this criterion. Details ▾Hide ▴

Evidence considered

ClinVar benign submission summary

Still missing

Primary evidence rather than assertion-based support would be needed.

Sources

clinvar ↗

Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AThis synonymous variant does not create a nonsense, frameshift, or canonical +/-1,2 splice-site change, so the generic PVS1 loss-of-function framework does not apply. Details ▾Hide ▴

Evidence considered

gene-level loss-of-function eligibility review
variant-level generic PVS1 scaffold
synonymous protein consequence p.Ala699=

Sources

pvs1_gene_contextpvs1_variant_assessmentpvs1_generic_framework ↗

PS1 N/APS1 is not applicable because this is a synonymous change and no alternate nucleotide change producing the same amino acid substitution is relevant here. Details ▾Hide ▴

Evidence considered

synonymous protein consequence p.Ala699=

PM4 N/APM4 is not applicable because this variant does not change protein length or disrupt an in-frame region. Details ▾Hide ▴

Evidence considered

synonymous protein consequence p.Ala699=

PM5 N/APM5 is not applicable because this is not a missense change, and the PM5 review artifact did not support classic same-residue comparator use for this variant. Details ▾Hide ▴

Evidence considered

PM5 candidate review marked classic same-residue logic ineligible

Sources

pm5_candidates

PP2 N/APP2 is not applicable because this is not a missense variant. Details ▾Hide ▴

Evidence considered

synonymous protein consequence p.Ala699=

BP1 N/ABP1 is not applicable because this is not a missense variant. Details ▾Hide ▴

Evidence considered

synonymous protein consequence p.Ala699=

BP3 N/ABP3 is not applicable because this variant is not an in-frame insertion or deletion in a repetitive region. Details ▾Hide ▴

Evidence considered

synonymous single-nucleotide substitution

BP4 N/ABP4 was not used because this is a synonymous variant; benign computational support for lack of splice effect is more appropriately captured under BP7. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score 0.00

Sources

spliceai ↗

Identifiers

Gene: TERT
Transcript: NM_198253.2
Coding (HGVS c.): NM_198253.2:c.2097C>T
Protein (HGVS p.): NP_937983.2:p.(Ala699=)
GRCh38: chr5:1279324 G>A
GRCh37: chr5:1279439 G>A
ClinVar: 39107
COSMIC: COSV57230878

Gene diagram

Every interpreted variant in TERT, mapped onto the exon structure of NM_198253.2. Select a row to find it on the plot.

TERTNM_198253.2

Fetching transcript structure from UCSC…

Exons

—

Transcript span

—

Strand

—

Variants mapped

—

Source

UCSC ncbiRefSeqCurated

All variants in TERT — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 14,255 / 1,585,702 alleles AF 0.00899 · 169 homozygotes · FAF 0.0493

gnomAD v2.1 2,562 / 230,130 alleles AF 0.0111 · 78 homozygotes · FAF 0.077

gnomAD-Canada v1.0 236 / 18,420 alleles AF 0.0128 · 5 homozygotes · FAF 0.0533

By genetic ancestry

gnomAD v4.1

AF 0.009 · 14255 / 1,585,702 alleles · 169 hom · FAF 0.049

East Asian2216 / 43,398	0.05191 hom
Amish12 / 912	0.013
Remaining individuals654 / 61,310	0.01113 hom
European (non-Finnish)10046 / 1,168,282	0.008653 hom
Ashkenazi Jewish209 / 29,092	0.0072
South Asian562 / 87,012	0.00658 hom
European (Finnish)213 / 60,676	0.0035
Admixed American196 / 56,046	0.00354 hom
Middle Eastern9 / 4,478	0.002
African/African American138 / 74,496	0.0019

gnomAD v2.1

AF 0.011 · 2562 / 230,130 alleles · 78 hom · FAF 0.077

East Asian1332 / 16,432	0.08168 hom
Remaining individuals47 / 6,206	0.0076
European (non-Finnish)764 / 101,172	0.00765 hom
Ashkenazi Jewish67 / 9,352	0.0072
South Asian152 / 25,940	0.00594 hom
European (Finnish)62 / 20,672	0.003
Admixed American90 / 30,550	0.00291 hom
African/African American48 / 19,806	0.0024

gnomAD-Canada

AF 0.013 · 236 / 18,420 alleles · 5 hom · FAF 0.053

fin1 / 8	0.12
eas86 / 1,338	0.0643 hom
oth16 / 1,138	0.014
sas13 / 1,362	0.0095
nfe111 / 11,742	0.00952 hom
amr5 / 838	0.006
asj4 / 832	0.0048

0 alternate alleles recorded in 2 other groups: afr, mid.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.00898971; MAF= 0.89897%, 14255/1585702 alleles, homozygotes = 169) and has highest observed frequency in the East Asian population (AF= 0.0510623; MAF= 5.10623%, 2216/43398 alleles, homozygotes = 91); grpmax FAF= 0.049291.

gnomAD v2.1

gnomAD-Canada

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat +33 bp

0.000

SpliceAI acceptor gainat -167 bp

0.000

SpliceAI donor lossat +295 bp

0.000

SpliceAI donor gainat -116 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

synonymous consequence
SpliceAI max delta score 0.00

Sources

spliceai ↗

PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact, with a maximum delta score of 0.00. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score 0.00

Sources

spliceai ↗

BP4 N/ABP4 was not used because this is a synonymous variant; benign computational support for lack of splice effect is more appropriately captured under BP7. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score 0.00

Sources

spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology.

Febbo PG et al. · 2011

No paper-specific finding is recorded.

PMID 22138009 ↗
A systematic approach to assessing the clinical significance of genetic variants.

No paper-specific finding is recorded.

PMID 24033266 ↗
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

No paper-specific finding is recorded.

PMID 25741868 ↗
PMID:20301408

No paper-specific finding is recorded.

PMID 20301408 ↗
Dyskeratosis Congenita and Related Telomere Biology Disorders.

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20301779 ↗
CEBPA-Associated Familial Acute Myeloid Leukemia (AML).

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20963938 ↗
Clinical utility gene card for: dyskeratosis congenita.

No paper-specific finding is recorded.

PMID 21610750 ↗
Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

Fey MF et al. · 2013

No paper-specific finding is recorded.

PMID 23970018 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

No paper-specific finding is recorded.

PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 14,255 / 1,585,702 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 16 Benign Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

ClinVar

This variant has been reported in ClinVar as Benign (16 clinical laboratories). (ClinVarID = 39107)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV57230878, n = 3 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.