Variant: NM_000314.7(PTEN):c.1212A>T (p.Ter404Cys)

CA10578936

234144 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: fc24cd5e-624d-4b84-b652-6f843664f53b

Approved on: 2019-11-22

Published on: 2019-12-11

HGVS expressions

NM_000314.7:c.1212A>T
NM_000314.7(PTEN):c.1212A>T (p.Ter404Cys)
NC_000010.11:g.87965472A>T
CM000672.2:g.87965472A>T
NC_000010.10:g.89725229A>T
CM000672.1:g.89725229A>T
NC_000010.9:g.89715209A>T
NG_007466.2:g.107034A>T
NM_000314.5:c.1212A>T
NM_000314.6:c.1212A>T
NM_001304717.2:c.1731A>T
NM_001304718.1:c.621A>T
NM_001304717.5:c.1731A>T
NM_001304718.2:c.621A>T
ENST00000371953.7:c.1212A>T

Pathogenic

• Met criteria codes: PS4_Moderate PM4 PM2 PS2

• Not Met criteria codes: PM1 PM5 PM6 BA1 BS1 BS3 BS4 BS2 BP5 BP7 BP4 BP2 PS3 PS1 PP1 PP2 PP3

Expert Panel

PTEN VCEP

Criteria Specification Information

Evidence submitted by expert panel

PTEN VCEP

PTEN c.1212A>T (p.Ter404CysextTer8) meets criteria to be classified as 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). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor ClinVar Organization ID: 26957) PM2: Absent in large sequenced populations (PMID 27535533). PM4: Variant causes protein extension. PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributors ClinVar Organization ID: 26957, SCV000278659.5)

Met criteria codes

• PS4_Moderate: Identified in a teenager with macrocephaly, thyroid cancer, and developmental delay (1 point) (Ambry Genetics). Confirmed de novo via exome (PS2) in a male child with autism and OFC +5SD (1 point) (GeneDx).
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: Absent in gnomAD (coverage >40X at this position).
• PS2: Confirmed de novo via exome (PS2) in a male child with autism and OFC +5SD (1 point) (GeneDx).

Not Met criteria codes

• PM1: 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
• 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
• 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
• 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
• BP4: 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
• 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
• 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