The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000314.7(PTEN):c.635-3C>G

CA645294060

427599 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 757c122c-05dc-41a9-bad0-40ff4ea79d3d
Approved on: 2023-10-11
Published on: 2023-10-18

HGVS expressions

NM_000314.7:c.635-3C>G
NM_000314.7(PTEN):c.635-3C>G
NC_000010.11:g.87957850C>G
CM000672.2:g.87957850C>G
NC_000010.10:g.89717607C>G
CM000672.1:g.89717607C>G
NC_000010.9:g.89707587C>G
NG_007466.2:g.99412C>G
ENST00000700029.2:c.635-3C>G
ENST00000710265.1:c.635-3C>G
ENST00000472832.3:c.635-3C>G
ENST00000688158.2:n.1370-3C>G
ENST00000688922.2:c.*465-3C>G
ENST00000700021.1:c.590-3C>G
ENST00000700022.1:c.493-3C>G
ENST00000700023.1:n.1793-3C>G
ENST00000700024.1:n.2027-3C>G
ENST00000700025.1:n.1404-3C>G
ENST00000700026.1:n.269C>G
ENST00000700029.1:c.469-3C>G
ENST00000706954.1:c.635-3C>G
ENST00000706955.1:c.*670-3C>G
ENST00000686459.1:c.*221-3C>G
ENST00000688158.1:c.*746-3C>G
ENST00000688308.1:c.635-3C>G
ENST00000688922.1:c.556-3C>G
ENST00000693560.1:c.1154-3C>G
ENST00000371953.8:c.635-3C>G
ENST00000371953.7:c.635-3C>G
ENST00000472832.2:c.62-3C>G
NM_000314.5:c.635-3C>G
NM_000314.6:c.635-3C>G
NM_001304717.2:c.1154-3C>G
NM_001304718.1:c.44-3C>G
NM_001304717.5:c.1154-3C>G
NM_001304718.2:c.44-3C>G
NM_000314.8:c.635-3C>G
More

Likely Pathogenic

Met criteria codes 4
PS4_Supporting PM6_Strong PM2_Supporting PP3
Not Met criteria codes 22
PM1 PM3 PM5 PM4 PVS1 BS1 BS4 BS3 BS2 BP5 BP7 BP4 BP3 BP1 BP2 PS1 PS2 PS3 BA1 PP1 PP2 PP4

Evidence Links 0

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
NM_000314.8(PTEN):c.635-3C>G (IVS6-3C>G) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria 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). PM2_P: Absent in large sequenced populations (PMID:27535533). PM6_S: One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. (PMID:19265751) PP3: SpliceAI predicts a splicing impact. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID:35278038)
Met criteria codes
PS4_Supporting
Leibowitz 2022: female child with neuroblastoma dx 16mo, angiosarcoma dx 4yo, lipoma, macrocephaly, another benign vascular malformation. TP53 negative. Peds score = 5, 1 PS4 point. (PMID: 35278038)
PM6_Strong
One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. Assumed de novo in a male 6 yr, 11 mo child with macrocephaly (58 cm) +4.2 SD, PDD, multiple small nevi, freckling of the glans penis. CC = 6 Varga EA et al. 2009 (PMID:19265751)
PM2_Supporting
Not present in gnomAD (coverage >60X).
PP3
SpliceAI in silico model predicts a splicing impact (acceptor loss 0.85, acceptor gain 0.69)
Not Met criteria codes
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
PVS1
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
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
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
PS1
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
PS3
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
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
PP4
Wrapped into PS4.
Curation History
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