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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

Variant: NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg)

CA130573

39808 (ClinVar)

Gene: PIK3R2
Condition: cerebral malformation
Inheritance Mode: Autosomal dominant inheritance (mosaic)
Link to MONDO
UUID: 421e7cec-5414-46bc-82b2-ecde31fd73a0
Approved on: 2021-03-01
Published on: 2021-09-27

HGVS expressions

NM_005027.4:c.1117G>A
NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg)
NC_000019.10:g.18162974G>A
CM000681.2:g.18162974G>A
NC_000019.9:g.18273784G>A
CM000681.1:g.18273784G>A
NC_000019.8:g.18134784G>A
NG_033010.1:g.14797G>A
NG_033010.2:g.14797G>A
ENST00000222254.13:c.1117G>A
ENST00000617130.5:c.*96G>A
ENST00000617642.2:c.*96G>A
ENST00000675271.1:n.63G>A
ENST00000222254.12:c.1117G>A
ENST00000426902.5:c.1117G>A
ENST00000593731.1:c.1117G>A
ENST00000617130.4:c.1117G>A
ENST00000617642.1:c.1117G>A
NM_005027.3:c.1117G>A
NR_073517.1:n.1657G>A
NR_073517.2:n.1672G>A
NR_162071.1:n.1455G>A
More

Pathogenic

Met criteria codes 5
PP2 PS2_Moderate PS4 PM2_Supporting PM1_Supporting
Not Met criteria codes 21
PP1 PP3 PP4 PS1 PS3 PM3 PM5 PM4 PM6 PVS1 BA1 BP4 BP3 BP1 BP2 BP5 BP7 BS2 BS1 BS4 BS3

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.1117G>A p.G373R missense variant in the PIK3R2 gene is previously reported in the literature and has been classified as PATHOGENIC. This variant has been confirmed de novo (PMID: 22729224) (PS2_Moderate). This variant has been identified in 2 individuals with macrocephaly (>=2 SD) and Developmental Delay or Intellectual disability with cortical malformation, 13 individuals with a clinical diagnosis of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome; (MPPH) or megalencephaly-capillary malformation-polymicrogyria syndrome; (MCAP), it has been shown to significantly increase phosphorylation levels in patient cell lines (PMID: 22729224 ), and has been identified in over 15 tumor samples in the literature and COSMIC (PMID: 28086757,22729224, 28502725 ) (PS4_Strong). This variant is located in the PIK3R2 SH2, sequence homology 2 domain (PM1). This variant is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org) (PM2). This gene has a low rate of benign missense changes (PP2).
Met criteria codes
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2_Moderate
13 MPPH (1 family w/ 3 affected sibs, parent was inferred to have germline mosaicism) PubMed:22729224
PS4
16 COSMIC, 27 cBioPortal This variant met criteria to meet PS4_VS >16
2 w/ OFC >2 SD, ventriculomegaly and PMG PubMed:28086757
13 w/ MPPH: hydrocephalus, ventriculomegaly and PMG PubMed:22729224
PM2_Supporting
absent from gnomAD and ExAC
PM1_Supporting
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Not Met criteria codes
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
PP4
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
PS3
patient derived cell lines showed increased PI3K activity and S6 phosphorylation versus control cells PubMed:22729224
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
PM6
13 MPPH (1 family w/ 3 affected sibs, parent was inferred to have germline mosaicism) PubMed:22729224
PVS1
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
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
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
BS2
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
patient derived cell lines showed increased PI3K activity and S6 phosphorylation versus control cells PubMed:22729224
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.