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]
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Variant: NM_000314.6(PTEN):c.-1195_-1184delAAGCCGCAGCAA

CA163819

189433 (ClinVar)

Gene: PTEN (HGNC:5728)
Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)
Inheritance Mode: Autosomal dominant inheritance
UUID: a4de2dba-9fd0-4e69-a9e5-2e6d4ec56af5
Approved on: 2019-03-05
Published on: 2019-07-23

HGVS expressions

NM_000314.6(PTEN):c.-1195_-1184delAAGCCGCAGCAA
NC_000010.11:g.87863274_87863285del
CM000672.2:g.87863274_87863285del
NC_000010.10:g.89623031_89623042del
CM000672.1:g.89623031_89623042del
NC_000010.9:g.89613011_89613022del
NG_007466.2:g.4837_4848del
NG_033079.1:g.5157_5168del
ENST00000706954.1:c.-17+632_-17+643del
ENST00000688308.1:c.-17+161_-17+172del
ENST00000445946.5:c.-794_-783del
ENST00000371953.7:c.-1196_-1185del
ENST00000445946.3:c.-794_-783del
NM_001126049.1:c.-794_-783del
NM_001126049.2:c.-794_-783del
More

Likely Benign

Met criteria codes 2
BP5 BS4_Supporting
Not Met criteria codes 23
BS2 BS1 BS3 BP7 BP4 BP3 BP1 BP2 PS1 PS2 PS3 PS4 PP1 PP2 PP3 PM1 PM3 PM5 PM4 PM6 PM2 PVS1 BA1

Evidence Links 6

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.-1195del12 (NC_000010.10:g.89623031_89623042delAAGCCGCAGCAA) meets criteria to be classified as likely benign 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). BS4_P: Lack of segregation in affected members of one family. (Internal laboratory contributor SCV SCV000222146.7) BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributors SCV000222146.7, SCV000183826.5)
Met criteria codes
BP5
Multiple co-occurrences from clinical laboratory contributors: SCV000222146.7, SCV000183826.5 - BRCA2, MSH6, MEN1, MLH1
BS4_Supporting
Consider BS4_P. GDx internal data: identified in teenage F with macrocephaly. Also present in teenage sister with normal OFC, no PHTS cutaneous features. NEGATIVE in teenage sister with macrocephaly (OFC 62.2cm), overgrowth, early puberty, no PHTS-related skin findings. Mother, 40s, also positive for variant, no clinical info.
Not Met criteria codes
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
Per previous EP review, results from this study not applicable for variant interpretation/criteria application. PubMed:21532617
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
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
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
Per previous EP review, results from this study not applicable for variant interpretation/criteria application. PubMed:21532617
PS4
Identified in a 19 year old Hispanic male jejunum carpeting of hamartomous polyps containing foveolar and gastric-type tissue with arborizing streaks of smooth muscle and minimal inflammation. NGS panel completed [APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53). Only finding was PTEN c.-1196_-1185del12. OFC 62cm but 6'2" and 225lbs, no derm/other PHTS findings. CC score = 26, 0.5 phenotype specificity points. PubMed:28157521
Variant listed in Table S2 as a pathogenic mutation identified in 2 individuals. A 58.2-year-old and a 59.1-year-old. Participants met relaxed ICC operational criteria per subjects and methods section. No additional patient specific information reported. PubMed:21194675
Identified in a cohort of premenopausal breast cancer patients who underwent oopherectomy PubMed:28821472
Variant listed as identified in this study in Supplementary Table 4. No additional patient specific information reported. Patients met full or relaxed criteria for Cowden syndrome per methods section. PubMed:25669429
Identified in 2 individuals. The first, a 53 year old female, reported to have a history of breast at 51 and thyroid cancer at 42. The second, a 57 year old female, with a history of breast cancer at 52 and no history of thyroid cancer. PubMed:21532617
Identified in 2 females. A 35-year-old, non-hispanic white, non-Ashkenazi Jewish, no personal history of cancer, family history of gynecologic and prostate cancers (CC score = 0). A 57-year-old, non-hispanic white, non-Ashkenazi Jewish, personal history of endometrial cancer, family history of other cancers (CC Score = 1. PubMed:28495237
PP1
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
4/31,374 global gnomAD alleles, N insufficient in subpopulations for benign criteria.
PVS1
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
Curation History
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