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]

Variant: NM_000314.8(PTEN):c.500C>A (p.Thr167Asn)

CA000487

39668 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 73986d71-3b36-4038-80e9-66da44231b6f
Approved on: 2023-06-14
Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.500C>A
NM_000314.8(PTEN):c.500C>A (p.Thr167Asn)
NC_000010.11:g.87952125C>A
CM000672.2:g.87952125C>A
NC_000010.10:g.89711882C>A
CM000672.1:g.89711882C>A
NC_000010.9:g.89701862C>A
NG_007466.2:g.93687C>A
ENST00000686459.1:c.*86C>A
ENST00000688158.1:c.*611C>A
ENST00000688308.1:c.500C>A
ENST00000688922.1:c.421C>A
ENST00000693560.1:c.1019C>A
ENST00000371953.8:c.500C>A
ENST00000371953.7:c.500C>A
NM_000314.5:c.500C>A
NM_000314.6:c.500C>A
NM_001304717.2:c.1019C>A
NM_001304718.1:c.-92C>A
NM_000314.7:c.500C>A
NM_001304717.5:c.1019C>A
NM_001304718.2:c.-92C>A
More

Likely Pathogenic

Met criteria codes 5
PP2 PP3 PM1 PM2_Supporting PM6
Not Met criteria codes 21
PS4 PS2 PS3 PS1 PP4 PP1 PVS1 PM3 PM4 PM5 BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 BP4

Evidence Links 2

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.500C>A (p.Thr167Asn) 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). PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. PM2_Supporting: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID:23160955) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score > 0.7 (score=0.751).
Met criteria codes
PP2
PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
PP3
REVEL score = 0.751, which is > 0.7 threshold.
PM1
PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. Impacts TI-loop (residues 166-168).
PM2_Supporting
Absent gnomAD
PM6
PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID:23160955)
Variant was de novo (parents tested via Sanger) in 8yo Hispanic F with autism, macrocephaly (OFC 56cm, +3SD), and NVIQ=77. Both parents and sister normal OFCs. Pt study ID 11390.p1. PubMed:23160955
Per JM Reports variant as de novo in pt with autism, but same study ID (11390) as pt in O'Roak, so seems likely to be same individual. Omit. PubMed:28250423
Not Met criteria codes
PS4
Variant was de novo (parents tested via Sanger) in 8yo Hispanic F with autism, macrocephaly (OFC 56cm, +3SD), and NVIQ=77. Both parents and sister normal OFCs. Pt study ID 11390.p1. Peds score = 4, but just has autism/macrocephaly so no points awarded. PubMed:23160955
PS2
Variant was de novo (parents tested via Sanger) in 8yo Hispanic F with autism, macrocephaly (OFC 56cm, +3SD), and NVIQ=77. Both parents and sister normal OFCs. Pt study ID 11390.p1. PubMed:23160955
Per JM Reports variant as de novo in pt with autism, but same study ID (11390) as pt in O'Roak, so seems likely to be same individual. Omit. PubMed:28250423
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
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
PVS1
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
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
Absent gnomAD
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
Absent gnomAD
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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