The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000314.6(PTEN):c.320A>T (p.Asp107Val)

CA16042748

372481 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: af7069ee-474b-491e-9317-5e91eeba5b76
Approved on: 2019-06-25
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.320A>T
NM_000314.6(PTEN):c.320A>T (p.Asp107Val)
NC_000010.11:g.87933079A>T
CM000672.2:g.87933079A>T
NC_000010.10:g.89692836A>T
CM000672.1:g.89692836A>T
NC_000010.9:g.89682816A>T
NG_007466.2:g.74641A>T
NM_000314.5:c.320A>T
NM_001304717.2:c.839A>T
NM_001304718.1:c.-431A>T
NM_000314.7:c.320A>T
NM_001304717.5:c.839A>T
NM_001304718.2:c.-431A>T
ENST00000371953.7:c.320A>T
ENST00000498703.1:n.146A>T
ENST00000610634.1:c.218A>T

Pathogenic

Met criteria codes 6
PM6 PM2 PS4_Moderate PS3 PP1 PP2
Not Met criteria codes 16
PM1 PM4 PM5 BA1 BS2 BS3 BS4 BS1 BP5 BP7 BP2 BP4 PVS1 PS2 PS1 PP3

Evidence Links 5

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.320A>T (p.Asp107Val) 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). PS3: Phosphatase activity <50% of wild type. (PMID 29706350) 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 25418537) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 28526761, PMID 23886400, internal laboratory contributor SCV000490750.2) PP1: Co-segregation with disease in multiple affected family members, with 3 or 4 meioses observed. (PMID 28526761, PMID 23886400, internal laboratory contributor SCV000490750.2) 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.
Met criteria codes
PM6
Variant occurred de novo in a child in the autism simplex cohort; methods appear to have been targeted to known candidate genes, not exome-based, but paper notes "paternity firmly established" via other variant info. May review with team to see whether would wish to apply PM6 or PS2. KS: Agrees and suggests applying PM6.

PM2
absent gnomAD. KS agrees.
PS4_Moderate
1 GDx internal case with peds score = 6, 1 phenotype point; in addition to other lit reports, 2.5 points total, moderate evidence. KS agrees.

PS3
KS agrees.

PP1
3 meioses total (1 Paparo, 1 Hansen-Kiss, 1 GDx internal family)

PP2
KS agrees.
Not Met criteria codes
PM1
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
KS: D107N, D107G, D107Y are present in HGMD, however already meets pathogenic so not necessary to work these up.
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
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
GeneDx internal data: Patient with PALB2 variant.
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
BP4
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
PS1
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
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