About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.413A>G, p.(Tyr138Cys)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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 ClinGen PTEN VCEP v3.2. 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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PS3Moderate
PS3 · moderate
Per PTEN VCEP specifications, PS3_Moderate is applied when phosphatase activity cumulative fitness score (Cum_score) ≤ -1.11 in the Mighell et al. 2018 (PMID:29706350) saturation mutagenesis assay. Y138C has a Cum_score of -1.766 in Table S2, meeting this threshold. Independently, Tibarewal et al. 2012 (PMID:22375056) directly characterized Y138C, demonstrating retained lipid phosphatase activity with selective loss of protein phosphatase activity and failure to suppress cellular invasion — consistent with a damaging functional effect.
PM2Supporting
PM2 · supporting
Per PTEN VCEP specifications, PM2_Supporting is applied when the variant is absent from population databases at allele frequency < 0.00001 (0.001%). NM_000314.8:c.413A>G is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0.
PP2Supporting
PP2 · supporting
Per PTEN VCEP specifications, PP2 applies to missense variants in PTEN, a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. PTEN is a well-established tumor suppressor with an observed deficit of benign missense variation and an established role for missense mutations in PHTS.
PP3Supporting
PP3 · supporting
Per PTEN VCEP specifications, PP3 is applied for missense variants when REVEL score > 0.7. The REVEL score for NM_000314.8:c.413A>G (p.Tyr138Cys) is 0.962, substantially exceeding the 0.7 threshold. BayesDel score is 0.518. SpliceAI max delta score is 0.00 (no predicted splicing impact).
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.2 v3.2 criteria-combination framework was evaluated deterministically with applied criteria: PS3 moderate, PM2 supporting, PP2 supporting, PP3 supporting; no rule matched the adjudicated criteria.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
3 Uncertain significance · 1 Uncertain Significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PTEN, a lipid and protein phosphatase, is one of the most frequently mutated genes in cancer.
COSMIC
Cancer Hotspots
Somatic evidence
6 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV64306562, n = 6 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PTEN VCEP v3.2, with the data and sources behind each one.
26 criteria with recorded statuses: 4 met · 9 not met · 6 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000314.8:c.413A>G (p.Tyr138Cys) is a missense variant in exon 5 of PTEN. It is absent from all population databases (gnomAD v2.1, v4.1, gnomAD-Canada), satisfying PM2_Supporting per PTEN VCEP criteria.
Functional evidence from Mighell et al. 2018 (PMID:29706350) saturation mutagenesis demonstrates that Y138C has a cumulative fitness score of -1.766, meeting the PTEN VCEP threshold of ≤ -1.11 for PS3_Moderate. Independently, Tibarewal et al. 2012 (PMID:22375056) characterized Y138C and demonstrated that it retains lipid phosphatase activity but selectively lacks protein phosphatase activity, with failure to suppress cellular invasion — confirming a damaging functional effect.
Computational evidence supports pathogenicity: REVEL score 0.962 (>0.7, meeting PP3 threshold per PTEN VCEP). PTEN has a low rate of benign missense variation and missense variants are a known disease mechanism for PTEN hamartoma tumor syndrome (PP2 per VCEP).
The variant is classified as Uncertain Significance in ClinVar (variation ID 486230) by all four submitting clinical laboratories. It has been observed in somatic cancers (COSMIC, n=6).
Applying the PTEN VCEP classification rules: 1 moderate pathogenic criterion (PS3_Moderate) and 3 supporting pathogenic criteria (PM2_Supporting, PP2, PP3) are met. No benign criteria are met. Per the VCEP combination rules, this evidence profile does not reach the Likely Pathogenic threshold (requires ≥3 moderate, or 2 moderate + ≥2 supporting, or 1 strong + 1 moderate, or 1 moderate + ≥4 supporting). The variant is classified as a Variant of Uncertain Significance (VUS).
Key gap: the Mighell et al. functional data for Y138C has a High_conf=False quality flag ('Fail Both'), indicating the measurement did not pass high-confidence filters. Additional functional validation, segregation data, de novo observations, or clinical case-level phenotype data could resolve this VUS.
No criteria match.
Met · 4
PS3 ModeratePer PTEN VCEP specifications, PS3_Moderate is applied when phosphatase activity cumulative fitness score (Cum_score) ≤ -1.11 in the Mighell et al. 2018 (PMID:29706350) saturation mutagenesis assay. Y138C has a Cum_score of -1.766 in Table S2, meeting this threshold. Independently, Tibarewal et al. 2012 (PMID:22375056) directly characterized Y138C, demonstrating retained lipid phosphatase activity with selective loss of protein phosphatase activity and failure to suppress cellular invasion — consistent with a damaging functional effect. Details ▾Hide ▴
Evidence considered
- Mighell et al. 2018 (PMID:29706350) PTEN saturation mutagenesis: Y138C Cum_score = -1.766
- meeting VCEP PS3_Moderate threshold of ≤ -1.11 (Table S2). Note: High_conf=False ('Fail Both') quality flag.
- Tibarewal et al. 2012 (PMID:22375056): Y138C retains lipid phosphatase activity but selectively lacks protein phosphatase activity
- fails to suppress U87MG glioma cell invasion in Matrigel
- shows increased Thr366 phosphorylation consistent with loss of autodephosphorylation activity.
Still missing
- High_conf=False in Mighell et al. assay (failed SE filter and high-confidence thresholds)
- confirmatory functional studies in germline context would strengthen evidence.
Sources
PM2 SupportingPer PTEN VCEP specifications, PM2_Supporting is applied when the variant is absent from population databases at allele frequency < 0.00001 (0.001%). NM_000314.8:c.413A>G is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes).
- Absent from gnomAD v4.1 (exomes).
- Absent from gnomAD-Canada v1.0 (genomes).
Sources
PP2 SupportingPer PTEN VCEP specifications, PP2 applies to missense variants in PTEN, a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. PTEN is a well-established tumor suppressor with an observed deficit of benign missense variation and an established role for missense mutations in PHTS. Details ▾Hide ▴
Evidence considered
- PTEN has a low rate of benign missense variation and missense variants are an established disease mechanism for PTEN hamartoma tumor syndrome (autosomal dominant).
Sources
PP3 SupportingPer PTEN VCEP specifications, PP3 is applied for missense variants when REVEL score > 0.7. The REVEL score for NM_000314.8:c.413A>G (p.Tyr138Cys) is 0.962, substantially exceeding the 0.7 threshold. BayesDel score is 0.518. SpliceAI max delta score is 0.00 (no predicted splicing impact). Details ▾Hide ▴
Evidence considered
- REVEL score 0.962 (>0.7 threshold per PTEN VCEP).
- BayesDel score 0.518 (above neutral but not independently diagnostic).
- SpliceAI max delta 0.00 (no splicing impact predicted).
Sources
Not met · 9 · evaluated, threshold not reached
PS1 PS1 requires that the same amino acid change (p.Tyr138Cys) has been previously established as pathogenic. In ClinVar (variation ID 486230), NM_000314.8:c.413A>G (p.Tyr138Cys) is classified as Uncertain Significance by all submitters. No prior pathogenic classification for this amino acid change exists. Details ▾Hide ▴
PM1 Per PTEN VCEP specifications, PM1 is restricted to residues within the defined catalytic motifs: 90-94, 123-130, and 166-168 (NP_000305.3). p.Tyr138 (position 138) lies outside these specified ranges. Although the variant lies in a statistically significant hotspot (cancerhotspots.org) and position 138 is within the phosphatase domain critical for protein phosphatase activity, the VCEP definition does not include residue 138. Details ▾Hide ▴
Evidence considered
- Position 138 is outside VCEP-defined catalytic motif ranges (90-94
- 123-130
- 166-168). Cancerhotspots.org identifies residue 138 as a statistically significant hotspot
- but VCEP PM1 definition is limited to specified catalytic motifs.
Sources
PM5 PM5 requires a different pathogenic or likely pathogenic missense change at the same amino acid residue (p.Tyr138). The PM5 candidate search identified no pathogenic/likely pathogenic missense variants at residue 138 in ClinVar. The only other missense variant identified at this position (Y138A in Mighell et al. Table S2) is not classified as pathogenic in ClinVar. Details ▾Hide ▴
Evidence considered
- No pathogenic or likely pathogenic missense variants at PTEN residue 138 in ClinVar. Y138A observed in saturation mutagenesis data but not classified as pathogenic.
Sources
pm5_candidatesclinvar ↗
BA1 Per PTEN VCEP, BA1 requires gnomAD filtering allele frequency > 0.00056 (0.056%). NM_000314.8:c.413A>G is absent from all gnomAD datasets (v2.1, v4.1, gnomAD-Canada). Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- v4.1
- and gnomAD-Canada
- does not meet BA1 frequency threshold.
Sources
BS1 Per PTEN VCEP, BS1 requires gnomAD filtering allele frequency from 0.000043 (0.0043%) to 0.00056 (0.056%). NM_000314.8:c.413A>G is absent from all gnomAD datasets, falling below the BS1 frequency range. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- v4.1
- and gnomAD-Canada
- does not meet BS1 frequency threshold.
Sources
BS2 Per PTEN VCEP, BS2 requires observation in the homozygous state in a healthy or PHTS-unaffected individual. No homozygous observations are reported in gnomAD or the literature for NM_000314.8:c.413A>G. Details ▾Hide ▴
Evidence considered
- No homozygous observations in any gnomAD dataset.
Sources
BS3 BS3 requires functional studies showing no damaging effect on protein function. The available functional data (Mighell et al. 2018 saturation mutagenesis, Cum_score = -1.766 ≤ -1.11; Tibarewal et al. 2012 showing loss of protein phosphatase activity and failure to suppress invasion) demonstrate a damaging effect, not a benign one. Per the PTEN VCEP, BS3_Supporting requires phosphatase activity > 0 — the observed Cum_score of -1.766 contradicts this. Details ▾Hide ▴
Evidence considered
- Mighell et al. 2018: Cum_score = -1.766
- indicating damaging effect (BS3 not met).
- Tibarewal et al. 2012: Y138C shows loss of protein phosphatase activity with selective functional defect.
Sources
BP2 Per PTEN VCEP, BP2 requires observation in trans with a pathogenic or likely pathogenic PTEN variant, or at least three observations in cis/phase unknown with different pathogenic/likely pathogenic PTEN variants. No such observations are reported for NM_000314.8:c.413A>G. Details ▾Hide ▴
Evidence considered
- No observations in trans or cis with pathogenic/likely pathogenic PTEN variants.
Sources
BP4 Per PTEN VCEP, BP4 is applied for missense variants when REVEL score < 0.5 (multiple lines of computational evidence suggest no impact). The REVEL score for NM_000314.8:c.413A>G is 0.962, which is above the 0.5 threshold and indicates a damaging prediction, not a benign one. Details ▾Hide ▴
Evidence considered
- REVEL score 0.962 (>0.5
- therefore does not meet BP4 threshold for benign prediction).
Sources
Not assessed · 6 · no assessment recorded
PS2 No de novo observation data is available in the evidence packet. None of the reviewed publications report a de novo occurrence of NM_000314.8:c.413A>G. Details ▾Hide ▴
Still missing
- No de novo data available for this variant.
PS4 No proband counts or case-control data are available to calculate a PTEN specificity score under the VCEP PS4 framework. The variant has been observed in ClinVar (4 clinical laboratory submissions, all VUS) and COSMIC (6 somatic occurrences), but these do not constitute proband data suitable for PS4 scoring. Details ▾Hide ▴
Evidence considered
- ClinVar: 4 submissions
- all Uncertain significance. COSMIC: 6 somatic occurrences (COSV64306562). No germline proband counts with phenotype data.
Still missing
- No proband phenotype data with specificity scoring available.
Sources
PM6 No de novo occurrence data is available in the evidence packet. None of the reviewed publications report a de novo observation of NM_000314.8:c.413A>G. Details ▾Hide ▴
Still missing
- No de novo data available for this variant.
PP1 No co-segregation data is available. None of the reviewed publications report family studies or meiotic segregation data for NM_000314.8:c.413A>G. Details ▾Hide ▴
Still missing
- No segregation or family data available.
BS4 No segregation data is available. None of the reviewed publications report family studies or lack of segregation for NM_000314.8:c.413A>G. Details ▾Hide ▴
Still missing
- No segregation data available.
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such data is available for NM_000314.8:c.413A>G. Details ▾Hide ▴
Still missing
- No data on alternate molecular diagnoses in carriers of this variant.
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000314.8:c.413A>G is a missense variant (p.Tyr138Cys); the PTEN VCEP PVS1 decision tree applies only to null variants (nonsense, frameshift, canonical splice site, CNV) and this variant does not fall into any of those buckets. Details ▾Hide ▴
Evidence considered
- Missense substitution in exon 5
- not a null variant eligible for PVS1 under PTEN VCEP decision tree.
Sources
PP4 VCEPThe PTEN VCEP explicitly states PP4 is Not Applicable; phenotype specificity has been incorporated into the PS4 rule specifications. Details ▾Hide ▴
Sources
PP5 VCEPThe PTEN VCEP explicitly states PP5 is Not Applicable. Additionally, ClinVar review status is 'criteria provided, single submitter' (1-star), which would not meet the 3-star expert panel threshold required for PP5 application even under generic ACMG/AMP. Details ▾Hide ▴
BP1 VCEPThe PTEN VCEP explicitly states BP1 is Not Applicable. Details ▾Hide ▴
Sources
BP6 VCEPThe PTEN VCEP explicitly states BP6 is Not Applicable. Details ▾Hide ▴
Sources
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond +7/-21 for which splicing prediction algorithms predict no impact. NM_000314.8:c.413A>G is a missense variant and is not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is restricted to synonymous and intronic variants.
Sources
PS5 N/APS5 is not a standard ACMG/AMP criterion and is not included in the PTEN VCEP specifications. Details ▾Hide ▴
Sources
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.413A>G
- Protein (HGVS p.)
- NP_000305.3:p.(Tyr138Cys)
- GRCh38
- chr10:87933172 A>G
- GRCh37
- chr10:89692929 A>G
- ClinVar
- 486230
- COSMIC
- COSV64306562
Gene diagram
Every interpreted variant in PTEN, mapped onto the exon structure of NM_000314.8. Select a row to find it on the plot.
PTENNM_000314.8
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 PTEN
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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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.962
- BayesDel
- 0.518
How the predictions were used
PP3 SupportingPer PTEN VCEP specifications, PP3 is applied for missense variants when REVEL score > 0.7. The REVEL score for NM_000314.8:c.413A>G (p.Tyr138Cys) is 0.962, substantially exceeding the 0.7 threshold. BayesDel score is 0.518. SpliceAI max delta score is 0.00 (no predicted splicing impact). Details ▾Hide ▴
Evidence considered
- REVEL score 0.962 (>0.7 threshold per PTEN VCEP).
- BayesDel score 0.518 (above neutral but not independently diagnostic).
- SpliceAI max delta 0.00 (no splicing impact predicted).
Sources
BP4 Per PTEN VCEP, BP4 is applied for missense variants when REVEL score < 0.5 (multiple lines of computational evidence suggest no impact). The REVEL score for NM_000314.8:c.413A>G is 0.962, which is above the 0.5 threshold and indicates a damaging prediction, not a benign one. Details ▾Hide ▴
Evidence considered
- REVEL score 0.962 (>0.5
- therefore does not meet BP4 threshold for benign prediction).
Sources
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond +7/-21 for which splicing prediction algorithms predict no impact. NM_000314.8:c.413A>G is a missense variant and is not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is restricted to synonymous and intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.962. BayesDel score = 0.518367.
8 paper records listed. 1 cited in the classification.
Cited in the classification
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PMID 22375056 ↗PTEN protein phosphatase activity correlates with control of gene expression and invasion, a tumor-suppressing phenotype, but not with AKT activity.Tibarewal P et al. · 2012 Feb 28Y138C (Tyr138Cys) was directly characterized as a tumor-derived PTEN mutant from small cell lung cancer cell line NCI-H196. When expressed in PTEN-null U87MG glioma cells, Y138C retained wild-type lipid phosphatase activity (suppressed PIP3 and AKT phosphorylation) but selectively lacked protein phosphatase activity and failed to suppress cellular invasion in Matrigel. Endogenous Y138C in NCI-H196 cells showed robust lipid phosphatase activity with little or no protein phosphatase activity and increased Thr366 phosphorylation, consistent with loss of autodephosphorylation. A second mutant at the same position, Y138L, showed identical properties.→ PS3 Names this variant
Source detail
we analyzed a PTEN Tyr138Cys (Y138C) mutant identified in a metastatic small cell lung cancer cell line, NCI-H196. When expressed, purified, and assayed in vitro, PTEN Y138C had catalytic properties like those of PTEN Y138L, displaying lipid phosphatase activity, but not protein phosphatase activity.
Location Results: 'A tumor-derived PTEN mutant...' section (pp. 5-7); Figure 6 and Figure 7
Context In vitro phosphatase assays with purified recombinant protein; lentiviral expression in PTEN-null U87MG glioblastoma cells; endogenous expression in NCI-H196 small cell lung cancer cells; Matrigel invasion assay; phosphospecific immunoblotting for Thr366
Other recorded publications
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PMID 32350270 ↗Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction.Multi-model functionalization study of 106 PTEN missense and nonsense variants associated with ASD, somatic cancer, and PHTS. The specific variant NM_000314.8:c.413A>G (p.Tyr138Cys) was not identified in this paper by any search term.Does not name this variant
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PMID 32366478 ↗A Premalignant Cell-Based Model for Functionalization and Classification of PTEN Variants.Premalignant cell-based model for functionalization and classification of PTEN variants. Only the frontmatter/copyright page was captured in the full-text file; the article body was not available. The variant NM_000314.8:c.413A>G was not identified in the available content.Does not name this variant
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PMID 23085752 ↗Disruption of epithelial architecture caused by loss of PTEN or by oncogenic mutant p110α/PIK3CA but not by HER2 or mutant AKT1.Berglund FM et al. · 2013Study of epithelial architecture disruption by PTEN loss, oncogenic PIK3CA, HER2, and AKT1 in breast cancer models. The specific variant NM_000314.8:c.413A>G (p.Tyr138Cys) was not identified in this paper.Does not name this variant
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PMID 25645574 ↗ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.ACG clinical guideline on genetic testing and management of hereditary gastrointestinal cancer syndromes. This is a clinical practice guideline and does not mention the specific variant NM_000314.8:c.413A>G.Does not name this variant
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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.ACMG/AMP standards and guidelines for variant interpretation. This is the foundational guideline document and does not contain variant-specific data for NM_000314.8:c.413A>G.Does not name this variant
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PMID 26450531 ↗Direct regulation of transforming growth factor β-induced epithelial-mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells.Kusunose M et al. · 2015Study of TGF-beta-induced EMT regulation by PTEN protein phosphatase activity in lung cancer cells. The specific variant NM_000314.8:c.413A>G (p.Tyr138Cys) was not identified in this paper.Does not name this variant
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PMID 26848951 ↗Differential Requirement for Pten Lipid and Protein Phosphatase Activity during Zebrafish Embryonic Development.Stumpf M et al. · 2016Study of differential requirement for Pten lipid and protein phosphatase activity during zebrafish embryonic development. The specific variant NM_000314.8:c.413A>G (p.Tyr138Cys) was not identified in this paper.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
3 Uncertain significance · 1 Uncertain Significance
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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637575
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/486230/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89692929-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87933172-A-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/10-87933172-A-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.413A…
- OncoKB ↗www.oncokb.org/gene/PTEN/Y138C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=139185296
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 486230)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.962. BayesDel score = 0.518367.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PTEN, a lipid and protein phosphatase, is one of the most frequently mutated genes in cancer.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV64306562, n = 6 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.