About TERT
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TERT c.2031C>T, p.(Gly677=)
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.
Words with a dotted underline have a short definition. Hover or tap them.
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 exceeds the benign stand-alone BA1 threshold of >1% in multiple datasets: gnomAD v2.1 AF is 1.18898%, gnomAD v4.1 AF is 1.12825%, and gnomAD-Canada AF is 1.04812%.
BS1Strong
BS1 · strong
Population frequency is also above the BS1 threshold of >0.3%, with gnomAD v2.1 AF 1.18898%, gnomAD v4.1 AF 1.12825%, and gnomAD-Canada AF 1.04812%.
BP7Supporting
BP7 · supporting
This is a synonymous variant with no predicted amino acid change, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, supporting no expected effect on splicing.
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
17,575 / 1,557,728 alleles
gnomAD v4.1: 17,575 / 1,557,728 alleles. Recorded AF 0.0112825. Recorded homozygote count 158.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0118898; MAF= 1.18898%, 2256/189742 alleles, homozygotes = 24) and has highest observed frequency in the African/African American population (AF= 0.0505191; MAF= 5.05191%, 837/16568 alleles, homozygotes = 13); grpmax FAF= 0.0500696.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0104812; MAF= 1.04812%, 193/18414 alleles, homozygotes = 0) and has highest observed frequency in the afr population (AF= 0.0558824; grpmax FAF95= 0.0442897).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
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
10 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV99721410, n = 10 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
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 · 3 not met · 14 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The TERT c.2031C>T (p.Gly677=) variant has been reported in ClinVar as benign by multiple clinical laboratories.
This variant is common in population databases, with allele frequencies above the BA1 benign threshold of 1% in gnomAD v2.1 (1.18898%), gnomAD v4.1 (1.12825%), and gnomAD-Canada (1.04812%).
This synonymous variant does not alter the encoded amino acid, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00.
No criteria match.
Met · 3
BA1 Stand alonePopulation frequency exceeds the benign stand-alone BA1 threshold of >1% in multiple datasets: gnomAD v2.1 AF is 1.18898%, gnomAD v4.1 AF is 1.12825%, and gnomAD-Canada AF is 1.04812%. Details ▾Hide ▴
Evidence considered
- The variant is common in large population datasets and well above the 1% benign threshold.
Sources
BS1 StrongPopulation frequency is also above the BS1 threshold of >0.3%, with gnomAD v2.1 AF 1.18898%, gnomAD v4.1 AF 1.12825%, and gnomAD-Canada AF 1.04812%. Details ▾Hide ▴
Evidence considered
- All available population datasets show frequency above the strong benign threshold.
Sources
BP7 SupportingThis is a synonymous variant with no predicted amino acid change, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, supporting no expected effect on splicing. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=)
- SpliceAI DS_AG 0.00
- DS_AL 0.00
- DS_DG 0.00
- DS_DL 0.00.
Sources
Not met · 3 · evaluated, threshold not reached
PM1 This variant was not identified in a statistically significant mutational hotspot or other established critical functional region without benign variation. Details ▾Hide ▴
Evidence considered
- Cancer Hotspots review did not identify a residue row or hotspot signal for Gly677.
Sources
PM2 Population frequency is far above the PM2 rarity threshold of <0.1%: gnomAD v2.1 AF is 1.18898%, gnomAD v4.1 AF is 1.12825%, and gnomAD-Canada AF is 1.04812%. Details ▾Hide ▴
Evidence considered
- The variant is common across population databases and therefore not rare.
Sources
PP3 Available computational evidence does not support a deleterious effect: SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and missense predictors such as REVEL and BayesDel were not available for this synonymous change. Details ▾Hide ▴
Evidence considered
- SpliceAI DS_AG 0.00
- DS_AL 0.00
- DS_DG 0.00
- DS_DL 0.00
- max delta score 0.00.
Sources
Not assessed · 14 · no assessment recorded
PS2 No confirmed de novo data were identified for this variant. Details ▾Hide ▴
Evidence considered
- No de novo evidence was provided.
Still missing
- Confirmed parental testing with phenotype information would be needed.
PS3 No validated functional studies demonstrating a damaging effect of this specific variant were identified. Details ▾Hide ▴
Evidence considered
- Curated oncology review did not provide variant-specific functional evidence for this synonymous change.
Still missing
- Well-established variant-specific functional data would be needed.
Sources
PS4 No case-control or case-enrichment data showing this variant is more common in affected individuals than in controls were identified. Details ▾Hide ▴
Evidence considered
- ClinVar contains benign submissions but no enrichment evidence.
Still missing
- Published enrichment data in a relevant germline disease cohort would be needed.
Sources
PM3 No evidence was identified showing this variant in trans with a pathogenic variant in a confirmed recessive disease setting. Details ▾Hide ▴
Evidence considered
- No trans observations were provided.
Still missing
- Phase-confirmed allelic data in an appropriate recessive context would be needed.
PM6 No assumed de novo evidence was identified for this variant. Details ▾Hide ▴
Evidence considered
- No de novo evidence was provided.
Still missing
- Reported de novo occurrence without full parental confirmation would be needed.
PP1 No segregation data were identified for this variant. Details ▾Hide ▴
Evidence considered
- No family segregation evidence was provided.
Still missing
- Segregation data in affected relatives would be needed.
PP4 No phenotype data were identified that are sufficiently specific to a disease caused by TERT variants to support PP4. Details ▾Hide ▴
Evidence considered
- No case-specific phenotype information was provided.
Still missing
- A specific
- well-documented phenotype highly consistent with TERT-related disease would be needed.
PP5 PP5 was not used because no independent reputable-source pathogenic assertion was identified that should be applied as stand-alone evidence. Details ▾Hide ▴
BS2 Although this variant is seen repeatedly in population databases, the available evidence does not directly establish observation in well-phenotyped unaffected individuals in a disease context suitable for BS2. Details ▾Hide ▴
Evidence considered
- Population databases include homozygotes
- but BS2 requires phenotype context that is not available here.
Still missing
- Well-documented unaffected adult observations in an appropriate penetrance framework would be needed.
Sources
BS3 No well-established functional studies demonstrating a normal effect of this specific variant were identified. Details ▾Hide ▴
Evidence considered
- No variant-specific benign functional study was identified.
Still missing
- Validated variant-specific functional data showing no damaging effect would be needed.
Sources
BS4 No segregation data showing lack of cosegregation with disease were identified. Details ▾Hide ▴
Evidence considered
- No family data were provided.
Still missing
- Family segregation data demonstrating non-segregation would be needed.
BP2 No phase data were identified to show this variant in trans with a pathogenic variant for a dominant disorder or in cis with a pathogenic variant in a way that would support BP2. Details ▾Hide ▴
Evidence considered
- No cis/trans data were provided.
Still missing
- Phase-confirmed allelic observations would be needed.
BP5 No alternate molecular diagnosis or other established cause was identified to explain a phenotype independently of this variant. Details ▾Hide ▴
Evidence considered
- No alternate diagnosis information was provided.
Still missing
- Case-level phenotype and alternate diagnosis data would be needed.
BP6 Although ClinVar contains multiple benign submissions, there is no expert-panel review or validated reputable-source evidence here that should be used as stand-alone BP6 evidence. Details ▾Hide ▴
Evidence considered
- ClinVar review status is criteria provided
- single submitter
- with no expert panel.
Still missing
- An expert-panel or otherwise validated reputable benign assertion would be needed.
Sources
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis synonymous variant does not create a premature stop, frameshift, or canonical +/-1,2 splice-site change, so the generic loss-of-function PVS1 framework does not apply. Details ▾Hide ▴
Evidence considered
- Generic PVS1 gene gate for TERT is eligible
- but the variant itself is outside the null-variant buckets used for default PVS1 application.
Sources
PS1 N/APS1 is for a different nucleotide change producing the same amino acid substitution as a known pathogenic variant, and this variant is synonymous with no amino acid substitution. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=).
PM4 N/APM4 applies to protein length changes from in-frame insertions/deletions or stop-loss variants, and this variant is a synonymous substitution. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=).
PM5 N/APM5 is a same-residue missense criterion, and this variant is synonymous; the PM5 candidate review also found no eligible classic same-residue comparator framework for use here. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvest was not eligible for classic same-residue missense application.
Sources
pm5_candidates
PP2 N/APP2 is a missense criterion and is not applicable to this synonymous variant. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=).
BP1 N/ABP1 is a missense criterion and is not applicable to this synonymous variant. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=).
BP3 N/ABP3 applies to in-frame insertions/deletions in repetitive regions without known function, and this variant is a synonymous substitution. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=).
BP4 N/ABP4 was not separately applied because this is a synonymous variant and the relevant computational evidence for a benign splicing effect is more appropriately captured under BP7; REVEL and BayesDel were not available for this change. Details ▾Hide ▴
Evidence considered
- SpliceAI predicts no significant splice effect
- missense predictors were not available for this synonymous variant.
Sources
Identifiers
- Gene
- TERT
- Transcript
- NM_198253.2
- Coding (HGVS c.)
- NM_198253.2:c.2031C>T
- Protein (HGVS p.)
- NP_937983.2:p.(Gly677=)
- GRCh38
- chr5:1279390 G>A
- GRCh37
- chr5:1279505 G>A
- ClinVar
- 227096
- COSMIC
- COSV99721410
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
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in TERT
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
17,575 / 1,557,728 alleles
AF 0.0113 · 158 homozygotes · FAF 0.0467
gnomAD v2.1
2,256 / 189,742 alleles
AF 0.0119 · 24 homozygotes · FAF 0.0501
gnomAD-Canada v1.0
193 / 18,414 alleles
AF 0.0105 · 0 homozygotes · FAF 0.0443
By genetic ancestry
gnomAD v4.1
AF 0.011 · 17575 / 1,557,728 alleles · 158 hom · FAF 0.047
| Amish72 / 912 | 0.0792 hom |
| African/African American3524 / 73,456 | 0.04874 hom |
| European (Finnish)731 / 58,950 | 0.0122 hom |
| Middle Eastern51 / 4,622 | 0.011 |
| Remaining individuals616 / 60,308 | 0.014 hom |
| European (non-Finnish)11723 / 1,152,686 | 0.0165 hom |
| Admixed American452 / 51,982 | 0.00871 hom |
| South Asian342 / 84,538 | 0.00410 hom |
| Ashkenazi Jewish56 / 28,718 | 0.0019 |
| East Asian8 / 41,556 | 0.00019 |
gnomAD v2.1
AF 0.012 · 2256 / 189,742 alleles · 24 hom · FAF 0.05
| African/African American837 / 16,568 | 0.05113 hom |
| European (Finnish)226 / 18,982 | 0.0121 hom |
| European (non-Finnish)850 / 77,562 | 0.0115 hom |
| Remaining individuals50 / 5,550 | 0.0091 hom |
| Admixed American199 / 26,128 | 0.0076 |
| South Asian81 / 23,106 | 0.00354 hom |
| Ashkenazi Jewish13 / 8,774 | 0.0015 |
0 alternate alleles recorded in 1 other group: East Asian.
gnomAD-Canada
AF 0.01 · 193 / 18,414 alleles · 0 hom · FAF 0.044
| afr57 / 1,020 | 0.056 |
| oth13 / 1,138 | 0.011 |
| nfe114 / 11,738 | 0.0097 |
| amr4 / 838 | 0.0048 |
| sas4 / 1,360 | 0.0029 |
| asj1 / 832 | 0.0012 |
0 alternate alleles recorded in 3 other groups: eas, fin, mid.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0112825; MAF= 1.12825%, 17575/1557728 alleles, homozygotes = 158) and has highest observed frequency in the Amish population (AF= 0.0789474; MAF= 7.89474%, 72/912 alleles, homozygotes = 2); grpmax FAF= 0.0466527.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0118898; MAF= 1.18898%, 2256/189742 alleles, homozygotes = 24) and has highest observed frequency in the African/African American population (AF= 0.0505191; MAF= 5.05191%, 837/16568 alleles, homozygotes = 13); grpmax FAF= 0.0500696.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0104812; MAF= 1.04812%, 193/18414 alleles, homozygotes = 0) and has highest observed frequency in the afr population (AF= 0.0558824; grpmax FAF95= 0.0442897).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP7 SupportingThis is a synonymous variant with no predicted amino acid change, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, supporting no expected effect on splicing. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Gly677=)
- SpliceAI DS_AG 0.00
- DS_AL 0.00
- DS_DG 0.00
- DS_DL 0.00.
Sources
PP3 Available computational evidence does not support a deleterious effect: SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and missense predictors such as REVEL and BayesDel were not available for this synonymous change. Details ▾Hide ▴
Evidence considered
- SpliceAI DS_AG 0.00
- DS_AL 0.00
- DS_DG 0.00
- DS_DL 0.00
- max delta score 0.00.
Sources
BP4 N/ABP4 was not separately applied because this is a synonymous variant and the relevant computational evidence for a benign splicing effect is more appropriately captured under BP7; REVEL and BayesDel were not available for this change. Details ▾Hide ▴
Evidence considered
- SpliceAI predicts no significant splice effect
- missense predictors were not available for this synonymous variant.
Sources
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
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PMID 22138009 ↗NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology.Febbo PG et al. · 2011No paper-specific finding is recorded.
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PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.No paper-specific finding is recorded.
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PMID 25741868 ↗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.
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PMID 20301408 ↗Pulmonary Fibrosis Predisposition Overview.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20301779 ↗Dyskeratosis Congenita and Related Telomere Biology Disorders.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20963938 ↗CEBPA-Associated Familial Acute Myeloid Leukemia (AML).Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 23970018 ↗Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Fey MF et al. · 2013No paper-specific finding is recorded.
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
17,575 / 1,557,728 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
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/227096/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/5-1279505-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr5-1279390-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/5-1279390-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_198253.2%3Ac.2031…
- OncoKB ↗www.oncokb.org/gene/TERT/G677=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=127097575
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0112825; MAF= 1.12825%, 17575/1557728 alleles, homozygotes = 158) and has highest observed frequency in the Amish population (AF= 0.0789474; MAF= 7.89474%, 72/912 alleles, homozygotes = 2); grpmax FAF= 0.0466527.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0118898; MAF= 1.18898%, 2256/189742 alleles, homozygotes = 24) and has highest observed frequency in the African/African American population (AF= 0.0505191; MAF= 5.05191%, 837/16568 alleles, homozygotes = 13); grpmax FAF= 0.0500696.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0104812; MAF= 1.04812%, 193/18414 alleles, homozygotes = 0) and has highest observed frequency in the afr population (AF= 0.0558824; grpmax FAF95= 0.0442897).
ClinVar
This variant has been reported in ClinVar as Benign (16 clinical laboratories). (ClinVarID = 227096)
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; COSV99721410, n = 10 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.