Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000314.8(PTEN):c.892C>G (p.Gln298Glu)

CA000623

127695 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 304beaf9-04a8-47e9-859a-ceb4b54a57fa
Approved on: 2023-08-04
Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.892C>G
NM_000314.8(PTEN):c.892C>G (p.Gln298Glu)
NC_000010.11:g.87960984C>G
CM000672.2:g.87960984C>G
NC_000010.10:g.89720741C>G
CM000672.1:g.89720741C>G
NC_000010.9:g.89710721C>G
NG_007466.2:g.102546C>G
ENST00000700029.2:c.985C>G
ENST00000710265.1:c.892C>G
ENST00000472832.3:c.892C>G
ENST00000688158.2:n.1627C>G
ENST00000688922.2:c.*722C>G
ENST00000700021.1:c.847C>G
ENST00000700022.1:c.*231C>G
ENST00000700023.1:n.2050C>G
ENST00000700024.1:n.2284C>G
ENST00000700025.1:n.1661C>G
ENST00000700026.1:n.529C>G
ENST00000706954.1:c.892C>G
ENST00000706955.1:c.*927C>G
ENST00000686459.1:c.*478C>G
ENST00000688158.1:c.*1003C>G
ENST00000688308.1:c.892C>G
ENST00000688922.1:c.813C>G
ENST00000693560.1:c.1411C>G
ENST00000371953.8:c.892C>G
ENST00000371953.7:c.892C>G
ENST00000472832.2:c.319C>G
NM_000314.5:c.892C>G
NM_000314.6:c.892C>G
NM_001304717.2:c.1411C>G
NM_001304718.1:c.301C>G
NM_000314.7:c.892C>G
NM_001304717.5:c.1411C>G
NM_001304718.2:c.301C>G
More

Likely Benign

Met criteria codes 4
PP2 BS3_Supporting BS1_Supporting BP4
Not Met criteria codes 21
PP1 PP3 PM1 PM3 PM5 PM4 PM6 PM2 PS1 PS2 PS3 PS4 BA1 PVS1 BP3 BP1 BP2 BP5 BP7 BS2 BS4

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
NM_000314.8(PTEN):c.892C>G (p.Gln298Glu) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BS1_Supporting: Filtering allele frequency of 0.00002132 (0.002132%, 4/24900 African/African American alleles) in gnomAD. BS3_Supporting: Massively parallel functional assay interrogating phosphatase activity demonstrating no statistically significant difference from wild type (PMID: 29706350). BP4: REVEL score = 0.229. PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. Variant with benign and pathogenic codes. Classification based on application of Bayesian Classification Framework (PMID: 29300386): BS1_P (-1 pt1), BS3_P (-1 pt), BP4 (-1 pt), PP2 (+1 pt) = -2 pts total (Likely Benign).
Met criteria codes
PP2
PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
BS3_Supporting
Mighell WT-like (0.30) results. Matreyek possibly wt-like (0.77) abundance class.
Variant abundance measured by massively parallel sequencing; in possibly wt-like abundance class (results 0.77). PubMed:29785012
High-throughput phosphatase assay; high-confidence score in WT-like range (results 0.30). PubMed:29706350
BS1_Supporting
Popmax FAF exome (0.00002132 [0.002132%]) within BS1_Supporting thresholds (0.00043% up to 0.0043%); no data quality issues
BP4
REVEL score = 0.229 (< 0.5)
Not Met criteria codes
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
ClinVar entries: c.892C>A (p.Gln298Lys) [ID: 570880]. 2 submitters (Invitae [VUS], Color [VUS]), and provided algorithm information reports variant may be tolerated. Variant not found in the literature. No reports of internal data. BLOSUM = 1. c.893A>C (p.Gln298Pro) [ID: 2105292]. 1 submitter (Invitae [VUS]), and provided algorithm information reports variant may be tolerated. Variant not found in the literature. No reports of internal data. BLOSUM = -1.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Global gnomAD frequency is too high to meet cut-off.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
KS changed criteria from "met" to "not met" based on Khan paper only investigating mutations with in silico models and not functional data. Khan paper (PMID, 26800850) listed variant as showing DDG values ranging from -0.05- -1.9, identified as less stable and deleterious nsSNPs using I-Mutant 2.0. This variant was not listed in the 5 found to be deleterious using combined computational tools.
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
KS changed from "met" to "not met" as there are not at least 2 cases to meet BP5. Yurgelun (2015) found variant in one indiv/1260 undergoing testing for Lynch syndrome. Indiv 1092248006 has variant and has pathogenic MLH1 mutation (dup exons 6-12)
Variant identified in 1 individual with a history of Lynch syndrome-associated cancer and/or polyps. Patient also harbored pathogenic MLH1 mutation (dup exons 6-12). PubMed:25980754
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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