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]
Link to SEPIO compliant JSON-LD document

Variant: NM_000314.6(PTEN):c.802delG (p.Asp268Thrfs)

CA000595

7839 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7fae3512-3b64-4560-8e0f-65a045970149

HGVS expressions

NM_000314.6:c.802delG
NM_000314.6(PTEN):c.802delG (p.Asp268Thrfs)
NC_000010.11:g.87960894del
CM000672.2:g.87960894del
NC_000010.10:g.89720651del
CM000672.1:g.89720651del
NC_000010.9:g.89710631del
NG_007466.2:g.102456del
ENST00000686459.1:c.*388del
ENST00000688158.1:c.*913del
ENST00000688308.1:c.802del
ENST00000688922.1:c.723del
ENST00000693560.1:c.1321del
ENST00000371953.8:c.802del
ENST00000371953.7:c.802del
ENST00000472832.2:c.229del
NM_000314.5:c.802del
NM_000314.6:c.802del
NM_001304717.2:c.1321del
NM_001304718.1:c.211del
NM_000314.7:c.802del
NM_001304717.5:c.1321del
NM_001304718.2:c.211del
NM_000314.8:c.802del

Likely Pathogenic

Met criteria codes 2
PM2_Supporting PVS1
Not Met criteria codes 24
BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 BP4 PM6 BA1 PM3 PM1 PM4 PM5 PS2 PS4 PS3 PS1 PP4 PP1 PP2 PP3

Evidence Links 1

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.802del (p.Asp268ThrfsTer8) variant meets criteria to be classified as likely pathogenic 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5’ to c.1121 (NM_000314.8). PM2_Supporting: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort (PMID:27535533).
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD (PM2_Supporting).
PVS1
Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5' to c.1121 (NM_000314.4).
Not Met criteria codes
BS4
Only 1 family reported with this variant in the literature, and article reports that patient is most likely a de novo occurrence even though parents were deceased and were unavailable for testing. No other family members had features of Cowden syndrome. PubMed:11238682
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Variant absent in gnomAD/ExAC; coverage kind of low though.
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
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
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
BP4
Not met because variant is incorrect variant type to apply criteria.
PM6
Only 1 family reported with this variant in the literature, and article reports that patient is most likely a de novo occurrence even though parents were deceased and were unavailable for testing. No other family members had features of Cowden syndrome. 1 sister tested negative for proband's mutation and no other family members underwent molecular analysis.
Only 1 family reported with this variant in the literature, and article reports that patient is most likely a de novo occurrence even though parents were deceased and were unavailable for testing. No other family members had features of Cowden syndrome. 1 sister tested negative for proband's mutation and no other family members underwent molecular analysis. PubMed:11238682
BA1
Variant absent in gnomAD/ExAC; coverage kind of low though.
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Variant not located within specified residues.
PM4
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
PS2
Only 1 family reported with this variant in the literature, and article reports that patient is most likely a de novo occurrence even though parents were deceased and were unavailable for testing. No other family members had features of Cowden syndrome. 1 sister tested negative for proband's mutation and no other family members underwent molecular analysis. PubMed:11238682
PS4
1 case report in the literature with no controls included.
1 case report in the literature with no controls included. PubMed:11238682
PS3
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
PP4
Identified in 41yo M (deceased at 43) with oral papillomas dx 31, trichilemmomas (?biopsy proven), macrocephaly (OFC not stated), "multi-organ" hamartomas, bronchiectasis, digital clubbing, R IDC dx 41. Minimum CC score = 12. PubMed:11238682
PP1
Only 1 family reported with this variant in the literature, and article reports that patient is most likely a de novo occurrence even though parents were deceased and were unavailable for testing. No other family members had features of Cowden syndrome.
Only 1 family reported with this variant in the literature, and article reports that patient is most likely a de novo occurrence even though parents were deceased and were unavailable for testing. No other family members had features of Cowden syndrome. PubMed:11238682
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Not met because variant is incorrect variant type to apply criteria.
Approved on: 2023-06-14
Published on: 2023-10-19
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