PTEN c.155_163del, p.Asp52_Arg55delinsGly
NM_000314.8:c.155_163del
Variant of Uncertain Significance (VUS)
The PTEN c.155_163del (D52_R55delinsG) variant is absent from population databases (PM2_Supporting) and causes an in-frame protein length change (PM4_Moderate). No additional evidence supports pathogenicity or benign impact. The combination of one Moderate and one Supporting criterion yields a classification of Variant of Uncertain Significance (VUS).
ACMG/AMP Criteria Applied
PM2
PM4
Genetic Information
Gene & Transcript Details
Gene
PTEN
Transcript
NM_000314.8
MANE Select
Total Exons
9
Strand
Forward (+)
Reference Sequence
NC_000010.10
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_000314.7 | RefSeq Select | 9 exons | Forward |
| NM_000314.5 | Alternative | 9 exons | Forward |
| NM_000314.4 | Alternative | 9 exons | Forward |
| NM_000314.3 | Alternative | 9 exons | Forward |
| NM_000314.6 | Alternative | 9 exons | Forward |
Variant Details
HGVS Notation
NM_000314.8:c.155_163del
Protein Change
D52_R55delinsG
Location
Exon 2
(Exon 2 of 9)
5'Exon Structure (9 total)3'
Functional Consequence
Loss of Function
Related Variants
Variant interpretation based on transcript NM_000314.8
Genome Browser
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HGVS InputNM_000314:c.155_163del
Active Tracks
ConservationRefSeqClinVargnomAD
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Clinical Data
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.05%
0.1%
1%
5%
10%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications (0)
No publication details.
Clinical Statement
Functional Impact
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Computational Analysis
Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific) VCEP Guidelines
PVS1
PVS1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PVS1 is: "Very Strong: Use PTEN PVS1 decision tree." The variant is an in-frame deletion/insertion not predicted to result in a null allele. Therefore, this criterion is not applied because the variant does not meet the null variant requirement.
PS1
PS1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PS1 is: "Strong: Same amino acid change as a previously established pathogenic variant regardless of nucleotide change." The variant does not result in a previously established pathogenic amino acid change. Therefore, PS1 is not applied.
PS2
PS2 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PS2 is: "Strong: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history." No de novo data are available. Therefore, PS2 is not applied.
PS3
PS3 (Not Applied) Strength Modified
According to PTEN Pre-processing, functional studies (PS3) were not available: "The PTEN D52_R55delinsG variant has not been functionally characterized." Therefore, PS3 is not applied due to lack of well-established functional evidence.
PS4
PS4 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PS4 is: "Strong: Prevalence in affected individuals significantly increased compared with controls or specificity score 4-15.5." No case data or specificity score are available. Therefore, PS4 is not applied.
PM1
PM1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM1 is: "Moderate: Located in a mutational hotspot or critical functional domain (residues 90-94,123-130,166-168)." The variant affects residues 52-55 outside of defined PTEN catalytic motifs. Therefore, PM1 is not applied.
PM2
PM2 (Supporting) Strength Modified
According to VCEP guidelines, the rule for PM2 is: "Supporting: Absent in population databases present at <0.00001 allele frequency in gnomAD." The variant is absent from gnomAD and other control databases. Therefore, PM2 is applied at Supporting strength because the variant is absent from controls.
PM3
PM3 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PM3 is: "Moderate: For recessive disorders, detected in trans with a pathogenic variant." No evidence of compound heterozygosity or trans configuration is available. Therefore, PM3 is not applied.
PM4
PM4 (Moderate)
According to VCEP guidelines, the rule for PM4 is: "Moderate: Protein length changes due to in-frame deletions/insertions in a non-repeat region." The variant causes an in-frame deletion/insertion of residues D52_R55delinsG, altering protein length. Therefore, PM4 is applied at Moderate strength.
PM5
PM5 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM5 is: "Moderate: Missense change at a residue where a different missense change is pathogenic." This variant is an in-frame indel, not a missense. Therefore, PM5 is not applied.
PM6
PM6 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM6 is: "Moderate: Assumed de novo without confirmation." No de novo assumptions are documented. Therefore, PM6 is not applied.
PP1
PP1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PP1 is: "Supporting: Co-segregation with disease in multiple affected family members (3-4 meioses)." No segregation data are available. Therefore, PP1 is not applied.
PP2
PP2 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PP2 is: "Supporting: Missense variant in a gene with low rate of benign missense variation where missense is common mechanism." This is an in-frame indel, not a missense. Therefore, PP2 is not applied.
PP3
PP3 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PP3 is: "Supporting: Multiple lines of computational evidence support deleterious effect (REVEL>0.7 or splicing concordance)." Computational predictions are inconclusive (SpliceAI max 0.39, no REVEL). Therefore, PP3 is not applied.
PP4
PP4 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PP4 is: "Supporting: Patient’s phenotype is highly specific for gene." No phenotype or case-specific data are provided. Therefore, PP4 is not applied.
PP5
PP5 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PP5 is: "Supporting: Reputable source reports variant as pathogenic." The variant is not found in ClinVar or other expert databases. Therefore, PP5 is not applied.
BA1
BA1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BA1 is: "Stand Alone: gnomAD allele frequency >0.00056." The variant is absent from population databases. Therefore, BA1 is not applied.
BS1
BS1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS1 is: "Strong: gnomAD allele frequency 0.000043–0.00056." The variant is absent from population databases. Therefore, BS1 is not applied.
BS2
BS2 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS2 is: "Strong: Observed homozygous in a healthy individual." No homozygous observations are reported. Therefore, BS2 is not applied.
BS3
BS3 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS3 is: "Strong: Well-established functional studies show no damaging effect." No functional studies are available. Therefore, BS3 is not applied.
BS4
BS4 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS4 is: "Strong: Lack of segregation in affected members of two or more families." No segregation data are available. Therefore, BS4 is not applied.
BP1
BP1 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for BP1 is: "Supporting: Missense in a gene where only truncating variants cause disease." This is an in-frame indel. Therefore, BP1 is not applied.
BP2
BP2 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP2 is: "Supporting: Observed in trans with a pathogenic variant." No such observations are available. Therefore, BP2 is not applied.
BP3
BP3 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP3 is: "Supporting: In-frame indels in repetitive region." The variant affects a non-repeat region. Therefore, BP3 is not applied.
BP4
BP4 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP4 is: "Supporting: Multiple lines of computational evidence suggest no impact (REVEL<0.5 or splicing concordance)." Computational evidence is inconclusive. Therefore, BP4 is not applied.
BP5
BP5 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP5 is: "Supporting: Variant found in a case with an alternate molecular basis." No alternate molecular basis is reported. Therefore, BP5 is not applied.
BP6
BP6 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for BP6 is: "Supporting: Reputable source reports as benign." The variant is not found in expert-curated benign listings. Therefore, BP6 is not applied.
BP7
BP7 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP7 is: "Supporting: Synonymous or intronic variant predicted no splicing impact." This is a coding in-frame indel. Therefore, BP7 is not applied.