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
  • See Evidence submitted by expert panel for details.

Variant: NM_000314.6(PTEN):c.-1084C>T

CA151479

127660 (ClinVar)

Gene: KLLN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e2f7ef05-08bd-4ef3-ace7-9e1121c35952

HGVS expressions

NM_000314.6:c.-1084C>T
NM_000314.6(PTEN):c.-1084C>T
NC_000010.11:g.87863385C>T
CM000672.2:g.87863385C>T
NC_000010.10:g.89623142C>T
CM000672.1:g.89623142C>T
NC_000010.9:g.89613122C>T
NG_007466.2:g.4948C>T
NG_033079.1:g.5053G>A
NM_001126049.1:c.-898G>A
ENST00000371953.7:c.-1085C>T
ENST00000445946.3:c.-898G>A

Likely Benign

Met criteria codes 3
BP2 BS1 BS2_Supporting
Not Met criteria codes 20
PM5 PM4 PM1 PS1 PS4 PS3 PS2 PM2 PM6 BA1 PVS1 BP7 BP5 BP4 BS4 BS3 PP3 PP2 PP1 PP4

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.-1084C>T (NC_000010.10:g.89623142C>T) 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). BS1: Allele frequency of 0.0025 (0.25%, 38/14,966 alleles) in the European subpopulation of the gnomAD cohort. (PMID 27535533) BP2: At least three observations in cis and/or phase unknown with different pathogenic/likely pathogenic PTEN variants. (internal laboratory contributor(s) SCV000149464.4) BS2_P: Meets criteria for BS2 (observed in the homozygous state in at least one healthy or PHTS-unaffected individual) but BS1 is also applied. (PMID 27884173, internal laboratory contributor(s) SCV000149464.4, SCV000185343.1)
Met criteria codes
BP2
4 internal GeneDx cases observed with different other PTEN PATH variants, phase unknown (2 nonsense, 1 canonical splice, 1 missense)
BS1
0.25% (38/14,966) allele frequency in European (Non-Finns) per gnomAD.
BS2_Supporting
Multiple homozygous observations in internal lab cases, 1 in older adult with no cancers in PTEN spectrum.
Variant appeared homozygous in multiple individuals lacking disease-related phenotype. PubMed:27884173
Not Met criteria codes
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
PS1
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
0.25% (38/14,966) allele frequency in European (Non-Finns) per gnomAD.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
0.25% (38/14,966) allele frequency in European (Non-Finns) per gnomAD.
PVS1
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
BP5
Multiple internal cases, but all with overlapping PHTS diagnoses, several in moderately penetrant genes.
BP4
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
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
PP1
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
Approved on: 2018-11-28
Published on: 2018-12-10
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