Variant: NM_000314.6(PTEN):c.740T>C (p.Leu247Ser)

CA16044135

223142 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 33e47859-5909-4f34-ac6c-c5bf41ab8544

Approved on: 2019-06-25

Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.740T>C
NM_000314.6(PTEN):c.740T>C (p.Leu247Ser)
NC_000010.11:g.87957958T>C
CM000672.2:g.87957958T>C
NC_000010.10:g.89717715T>C
CM000672.1:g.89717715T>C
NC_000010.9:g.89707695T>C
NG_007466.2:g.99520T>C
ENST00000700029.2:c.740T>C
ENST00000710265.1:c.740T>C
ENST00000472832.3:c.740T>C
ENST00000688158.2:n.1475T>C
ENST00000688922.2:c.*570T>C
ENST00000700021.1:c.695T>C
ENST00000700022.1:c.*79T>C
ENST00000700023.1:n.1898T>C
ENST00000700024.1:n.2132T>C
ENST00000700025.1:n.1509T>C
ENST00000700026.1:n.377T>C
ENST00000700029.1:c.574T>C
ENST00000706954.1:c.740T>C
ENST00000706955.1:c.*775T>C
ENST00000686459.1:c.*326T>C
ENST00000688158.1:c.*851T>C
ENST00000688308.1:c.740T>C
ENST00000688922.1:c.661T>C
ENST00000693560.1:c.1259T>C
ENST00000371953.8:c.740T>C
ENST00000371953.7:c.740T>C
ENST00000472832.2:c.167T>C
NM_000314.5:c.740T>C
NM_001304717.2:c.1259T>C
NM_001304718.1:c.149T>C
NM_000314.7:c.740T>C
NM_001304717.5:c.1259T>C
NM_001304718.2:c.149T>C
NM_000314.8:c.740T>C

Likely Pathogenic

• Met criteria codes: PP2 PS4_Supporting PM6 PM2

• Not Met criteria codes: PP1 PP3 PP4 PM1 PM3 PM5 PM4 BA1 BS2 BS1 BS4 BS3 PS1 PS2 PS3 PVS1 BP5 BP7 BP4 BP3 BP1 BP2

Expert Panel

PTEN VCEP

Criteria Specification Information

Evidence submitted by expert panel

PTEN VCEP

PTEN c.740T>C (p.Leu247Ser) meets criteria to be classified as likely pathogenic 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). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 28086757) 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. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 28086757)

Met criteria codes

• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4_Supporting: Proband specificity score of 5 for child = 1 point
• PM6: Negishi et al reported that patient #5 had variant as confirmed de novo event. - JMester agree, added PMID. Also added Kato et al. reference although likely same patient - MPerpich
• PM2: Variant not found in gnomAD.

Not Met criteria codes

• 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
• PP4: Patient #5 described in paper by Negishi et al is a 4.9mo female who has an OFC of 4.3 SD and developmental delay. Proband specificity score is 5 so PP4 can be applied. - JM agree but added to PS4 instead of PP4.
• 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
• 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
• 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
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: Mighell et al. lipid phosphatase activity is -1.669765892 therefore in the hypomorphic range (no criteria can be applied). - JM agree
• PVS1: 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
• 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