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_000314.7(PTEN):c.1027-4C>G

CA000260

142878 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3238b347-e5f0-45ed-b567-0d87ea48b9c2
Approved on: 2023-12-01
Published on: 2023-12-18

HGVS expressions

NM_000314.7:c.1027-4C>G
NM_000314.7(PTEN):c.1027-4C>G
NC_000010.11:g.87965283C>G
CM000672.2:g.87965283C>G
NC_000010.10:g.89725040C>G
CM000672.1:g.89725040C>G
NC_000010.9:g.89715020C>G
NG_007466.2:g.106845C>G
ENST00000686459.1:c.*613-4C>G
ENST00000688158.1:c.*1138-4C>G
ENST00000688308.1:c.1027-4C>G
ENST00000688922.1:c.948-4C>G
ENST00000693560.1:c.1546-4C>G
ENST00000371953.8:c.1027-4C>G
ENST00000371953.7:c.1027-4C>G
NM_000314.5:c.1027-4C>G
NM_000314.6:c.1027-4C>G
NM_001304717.2:c.1546-4C>G
NM_001304718.1:c.436-4C>G
NM_001304717.5:c.1546-4C>G
NM_001304718.2:c.436-4C>G
NM_000314.8:c.1027-4C>G
NM_000314.8(PTEN):c.1027-4C>G

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 25
BP5 BP7 BP2 BP3 BP1 PS2 PS4 PS3 PS1 PVS1 PP4 PP1 PP3 PP2 PM6 PM2 PM3 PM1 PM4 PM5 BA1 BS4 BS3 BS1 BS2

Evidence Links 0

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
PTEN c.1027-4C>G (IVS8-4C>G) is currently classified as a variant of uncertain significance 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). BP4: Intronic variant where at least 2 out of 3 in silico models predict no splicing impact.
Met criteria codes
BP4
Intronic variant where at least 2 out of 3 in silico models predict no splicing impact. SpliceAI: GeneDx: no or low splice effect (0.00 or 0.02) HSF: WT 90.58 pos 89; MUT no impact, pos 89 -0.68%, downstream potential cryptic a little weaker 72.79, WT was 75.16 MaxEnt: WT 11.86 pos 81; MUT a little weaker -9.95%, no cryptic predicted, not significant NNsplice: WT 1.00 pos 30, MUT no impact.
Not Met criteria codes
BP5
1 GeneDx internal case: adult male with myelodysplastic syndrome and immunodeficiency, WES diagnostic for GATA2.  Need another case to meet BP5.
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
PS2
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
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
PP2
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
AF=0.00006092 in Remaining population (2/32832) in gnomAD 4.0 AF=0.00002316 in Admixed American population (1/43180) gnomAD 4.0
PM3
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
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
BA1
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
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
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
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