Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • See Evidence submitted by expert panel for details.

Variant: NM_005027.4:c.320C>T

CA9306690

1296987 (ClinVar)

Gene: PIK3R2
Condition: overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance Mode: Autosomal dominant inheritance (mosaic)
Link to MONDO
UUID: ae588dd0-d428-4731-aeb8-12c56c022c9e

HGVS expressions

NM_005027.4:c.320C>T
NC_000019.10:g.18156199C>T
CM000681.2:g.18156199C>T
NC_000019.9:g.18267009C>T
CM000681.1:g.18267009C>T
NC_000019.8:g.18128009C>T
NG_033010.1:g.8022C>T
NG_033010.2:g.8022C>T
ENST00000222254.13:c.320C>T
ENST00000617130.5:c.320C>T
ENST00000617642.2:c.320C>T
ENST00000222254.12:c.320C>T
ENST00000426902.5:c.320C>T
ENST00000593731.1:c.320C>T
ENST00000617130.4:n.320C>T
ENST00000617642.1:n.320C>T
NM_005027.3:c.320C>T
NR_073517.1:n.860C>T
NR_073517.2:n.875C>T
NR_162071.1:n.875C>T
NM_005027.4(PIK3R2):c.320C>T (p.Pro107Leu)

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 1
BS1
Not Met criteria codes 25
BP5 BP7 BP2 BP3 BP4 BP1 BA1 PM3 PM1 PM4 PM5 PM6 PM2 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PVS1 BS4 BS3 BS2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.320C>T (NM_005027.4) variant in PIK3R2 is a missense variant predicted to cause substitution of (p.Pro107Leu). The highest population minor allele frequency in gnomAD v2.1.1 is 0.001838 in the European (Finnish) population, which is higher than the ClinGen BMEP threshold ([>0.00037]) for BS1, and therefore meets this criterion (BS1). In summary, this variant meets the criteria to be classified as Likely benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BS1; -4 points (VCEP specifications version 1; Approved: 1/31/2021)
Met criteria codes
BS1
The variant is present in 28/15236 Finnish alleles (0.1838%) and one homozygous observation in gnomAD.
Not Met criteria codes
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
BA1
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
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
PS4
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
PP4
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
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
The missense Z score for PIK3R2 is z=2.48
PVS1
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
Approved on: 2022-02-12
Published on: 2022-02-12
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