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_181690.2(AKT3):c.49G>A (p.Glu17Lys)

CA130584

39816 (ClinVar)

Gene: AKT3
Condition: cerebral malformation
Inheritance Mode: Autosomal dominant inheritance (mosaic)
Link to MONDO
UUID: 0c491a99-6d6d-43fa-8837-da81e69e236b
Approved on: 2021-01-31
Published on: 2021-09-27

HGVS expressions

NM_181690.2:c.49G>A
NM_181690.2(AKT3):c.49G>A (p.Glu17Lys)
NC_000001.11:g.243695714C>T
CM000663.2:g.243695714C>T
NC_000001.10:g.243859016C>T
CM000663.1:g.243859016C>T
NC_000001.9:g.241925639C>T
NG_029764.1:g.152871G>A
NG_029764.2:g.160366G>A
ENST00000263826.12:c.49G>A
ENST00000366539.6:c.49G>A
ENST00000491219.6:c.43G>A
ENST00000492957.2:c.49G>A
ENST00000552631.2:n.163G>A
ENST00000672238.1:c.49G>A
ENST00000672442.1:c.49G>A
ENST00000672578.1:c.-135G>A
ENST00000672679.1:n.6G>A
ENST00000673400.1:c.49G>A
ENST00000673466.1:c.49G>A
ENST00000680056.1:c.47-30831G>A
ENST00000680118.1:c.49G>A
ENST00000681794.1:c.49G>A
ENST00000263826.9:c.49G>A
ENST00000336199.9:c.49G>A
ENST00000366539.5:c.49G>A
ENST00000366540.5:c.49G>A
ENST00000463991.5:n.187G>A
ENST00000490018.1:n.541G>A
ENST00000491219.5:n.3G>A
ENST00000552631.1:c.49G>A
NM_001206729.1:c.49G>A
NM_005465.4:c.49G>A
NM_005465.5:c.49G>A
NM_001370074.1:c.49G>A
NM_005465.7:c.49G>A
NM_001206729.2:c.49G>A
More

Pathogenic

Met criteria codes 6
PS4 PS2_Moderate PM1_Supporting PP2 PM2 PS3_Supporting
Not Met criteria codes 20
BA1 BS2 BS1 BS4 BS3 BP4 BP3 BP1 BP2 BP5 BP7 PS1 PP1 PP3 PP4 PVS1 PM6 PM3 PM5 PM4

Evidence Links 4

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.49G>A p.E17K in the AKT3 gene is previously reported in the literature and has been classified as PATHOGENIC. Testing of unaffected and affected tissue show variable allelic fractions consistent with a post-zygotic event (PMID: 22500628) (PS2_Moderate).This variant has been shown to significantly increase phosphorylation levels in experiments with case and controls cells of similar isogenic backgrounds (PMID: 18813315) (PS3_supporting). This variant has been identified in 4 individuals with neuroimaging demonstrating at least one large cerebral hemisphere with cortical malformation(s) and 7 tumor samples in the literature and COSMIC (PMID: 28969385, PMID: 22500628 PMID:22729223) (PS4_Strong). This variant is located in the AKT3 pleckstrin homology 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
PS4
In 7 COSMIC tumor samples
LR15-262 HMW w/contralateral hemimicroencephaly & capillary malformations; LR16-251 megalencephaly w/multifocal but bilateral cortical malformations; LR11-443 one enlarged cerebral hemisphere with dysplasia identified in the contralteral hemisphere PubMed:28969385
HME PubMed:22729223
PS2_Moderate
patient with HME: 17% of clones (35% of brain cells) absent from blood. PubMed:22500628
PM1_Supporting
pleckstrin homology domain
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
absent from gnomAD and ExAC
PS3_Supporting
generated cell lines, increased AKT phosphorylation PubMed:18813315
Not Met criteria codes
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
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
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
PS1
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
PP4
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
PM6
patient with HME: 17% of clones (35% of brain cells) absent from blood. PubMed:22500628
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
Curation History
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