The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Criteria Specification: CSpec Registry PDF

Variant: NM_000314.6(PTEN):c.75G>A (p.Leu25=)

CA000197

184505 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: e5e35031-cdfe-44ec-ad5e-0f3892c0a7b1

HGVS expressions

NM_000314.6:c.75G>A
NM_000314.6(PTEN):c.75G>A (p.Leu25=)
NC_000010.11:g.87864544G>A
CM000672.2:g.87864544G>A
NC_000010.10:g.89624301G>A
CM000672.1:g.89624301G>A
NC_000010.9:g.89614281G>A
NG_007466.2:g.6106G>A
NG_033079.1:g.3894C>T
NM_000314.5:c.75G>A
NM_001304717.2:c.594G>A
NM_001304718.1:c.-631G>A
NM_000314.7:c.75G>A
NM_001304717.5:c.594G>A
NM_001304718.2:c.-631G>A
ENST00000371953.7:c.75G>A
ENST00000462694.1:n.77G>A
ENST00000487939.1:n.96G>A
ENST00000610634.1:c.-28G>A
ENST00000618586.1:n.44G>A

Uncertain Significance

Met criteria codes 2
PM2 BP7
Unmet criteria codes 20
PVS1 PM5 PM4 PM1 PM6 BA1 BS2 BS1 BS3 BS4 BP5 BP4 BP2 PS1 PS3 PS4 PS2 PP2 PP3 PP1

Expert Panel

Evidence Links 0

Evidence submitted by expert panel
PTEN VCEP
PTEN c.75G>A (p.Leu25=) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). BP7: Variant is synonymous (silent), nucleotide is not conserved, and no splicing impact is predicted.
Met criteria codes
PM2
Absent gnomAD. I agree (FH)
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Unmet criteria codes
PVS1
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
PM1
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
BA1
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
BS1
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
BS4
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
BP4
In silico predictors unable to provide prediction for nearby SDS.
BP2
1 internal lab observation in cis with D24N (LPATH per this lab), need 3 observations in cis or phase unknown with different variants to apply BP2.
PS1
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
1 internal case from CCF PTEN study with CC Score of 22. OFC: unknown; Papillary Thyroid Carcinoma dx age 15; Fibrocystic Breast Disease; Left breast cancer, dx 37- ductal carcinoma + left DCIS (cribriform), mastectomy; Fibroadenoma of Breast; Uterine Fibroids; Fibroma; Oral Mucosa Papilloma. Doesn't meet criteria for PS4, PS4_moderate, or PS4_supporting.
PS2
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
PP3
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
Approved on: 2019-06-25
Published on: 2019-07-23
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