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_000314.7(PTEN):c.610C>G (p.Pro204Ala)

CA000535

189415 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: b5627c7e-eb93-4a97-95aa-58fd645e077c
Approved on: 2023-10-11
Published on: 2023-10-18

HGVS expressions

NM_000314.7:c.610C>G
NM_000314.7(PTEN):c.610C>G (p.Pro204Ala)
NC_000010.11:g.87952235C>G
CM000672.2:g.87952235C>G
NC_000010.10:g.89711992C>G
CM000672.1:g.89711992C>G
NC_000010.9:g.89701972C>G
NG_007466.2:g.93797C>G
ENST00000686459.1:c.*196C>G
ENST00000688158.1:c.*721C>G
ENST00000688308.1:c.610C>G
ENST00000688922.1:c.531C>G
ENST00000693560.1:c.1129C>G
ENST00000371953.8:c.610C>G
ENST00000371953.7:c.610C>G
ENST00000472832.2:c.37C>G
NM_000314.5:c.610C>G
NM_000314.6:c.610C>G
NM_001304717.2:c.1129C>G
NM_001304718.1:c.19C>G
NM_001304717.5:c.1129C>G
NM_001304718.2:c.19C>G
NM_000314.8:c.610C>G
NM_000314.8(PTEN):c.610C>G (p.Pro204Ala)

Pathogenic

Met criteria codes 6
PS3_Moderate PM2_Supporting PM6_Strong PP3 PP2 PS4_Supporting
Not Met criteria codes 20
BS3 BS4 BS1 PVS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS1 BA1 PP4 PP1 PM3 PM1 PM4 PM5

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.610C>G (p.Pro204Ala) meets criteria to be classified as 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). PM6_S: One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. (internal laboratory contributor SCV000222125.7) PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -1.675 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor SCV000222125.7) PM2_P: Absent in large sequenced populations (PMID 27535533). 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 of this variant = 0.881)
Met criteria codes
PS3_Moderate
Mighell score hypomorphic

PM2_Supporting
Absent gnomAD
PM6_Strong
GDx #1 assumed de novo; patient with high phenotype specificity (meets PS4_P), data combined to upweight here.
PP3
Score = 0.881
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4_Supporting
GDx #1: F child extreme macro and autism, peds score = 5, 1 phenotype point. GDx #2: M child macro NOS and DD; mother pos macro 59cm and thy nod CC score 10. Assumed de novo, PS4_P wrapped into PM6_S upweight. GDX #2: male child with extreme macroceph (+5.5SD), delays. Inherited from HET mother with macrocephaly, thyroid nodules. Meets PS4_P, 1 meiosis towards PP1.
Not Met criteria codes
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
BS1
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
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
BP4
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
PS2
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
BA1
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
1 meiosis from GDx #2, described in PS4_P
PM3
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
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
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