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.1061C>A (p.Pro354Gln)

CA000275

143020 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: e75a40b0-8e18-418e-b6c7-079646958d18
Approved on: 2023-06-14
Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.1061C>A
NM_000314.8(PTEN):c.1061C>A (p.Pro354Gln)
NC_000010.11:g.87965321C>A
CM000672.2:g.87965321C>A
NC_000010.10:g.89725078C>A
CM000672.1:g.89725078C>A
NC_000010.9:g.89715058C>A
NG_007466.2:g.106883C>A
ENST00000700029.2:c.1154C>A
ENST00000710265.1:c.*90C>A
ENST00000688158.2:n.1796C>A
ENST00000688922.2:c.*891C>A
ENST00000700021.1:c.1016C>A
ENST00000700022.1:c.*400C>A
ENST00000700023.1:n.2219C>A
ENST00000700024.1:n.2453C>A
ENST00000706954.1:c.1061C>A
ENST00000706955.1:c.*1096C>A
ENST00000686459.1:c.*647C>A
ENST00000688158.1:c.*1172C>A
ENST00000688308.1:c.1061C>A
ENST00000688922.1:c.982C>A
ENST00000693560.1:c.1580C>A
ENST00000371953.8:c.1061C>A
ENST00000371953.7:c.1061C>A
NM_000314.5:c.1061C>A
NM_000314.6:c.1061C>A
NM_001304717.2:c.1580C>A
NM_001304718.1:c.470C>A
NM_000314.7:c.1061C>A
NM_001304717.5:c.1580C>A
NM_001304718.2:c.470C>A
More

Likely Benign

Met criteria codes 4
BS1 BP4 BS3_Supporting PP2
Not Met criteria codes 22
BS2 BS4 BP3 BP1 BP2 BP5 BP7 PM6 PM2 PM1 PM3 PM5 PM4 PS1 PS2 PS3 PS4 BA1 PP1 PP3 PP4 PVS1

Evidence Links 7

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.1061C>A (p.Pro354Gln) variant 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: To be applied for variants with filtering allele frequency (FAF) of 0.000043 up to 0.00056 (0.0043% up to 0.056%) in gnomAD. Popmax FAF of this variant=0.0001051. BS3_P: In vitro or in vivo functional study or studies showing no damaging effect on protein function. This variant: score of 0.09 (WT-like range) on high throughput phosphatase assay (PMID:29706350). BP4: REVEL score < 0.5 (score=0.497). 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. Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign strong and 2 benign supporting = -6. 1 pathogenic supporting = 1. Total = – 5 (likely benign).
Met criteria codes
BS1
gnomAD v2.1.1: 19/125384 (.0115%) European/non-Finnish pop (.00011515). Popmax Filtering AF is .0001051 which meets BS1 criteria [gnomAD Filtering allele frequency from 0.000043 (0.0043%) up to 0.00056 (0.056%)].
BP4
REVEL score < 0.5 (score=0.497)
BS3_Supporting
In vitro or in vivo functional study or studies showing no damaging effect on protein function. Score of 0.09 (WT-like range) on high throughput phosphatase assay (PMID:29706350).

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.
Not Met criteria codes
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
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
Some cases suggestive, but overlapping phenotypes with PHTS
BP7
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
0.015% (19/122,896) European (Non-Finnish) alleles in gnomAD; 3/1886 alleles in GME variome.
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
0.015% (19/122,896) European (Non-Finnish) alleles in gnomAD; 3/1886 alleles in GME variome.
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
PP4
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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