Evidence Repository - Clinical Genome Resources

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_005249.4(FOXG1):c.460dupG (p.Glu154Glyfs)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA199435

95268 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 432bce4a-6af0-46d5-9832-aec186137890

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_005249.4:c.460dupG

NM_005249.4:c.460dup

NM_005249.4(FOXG1):c.460dupG (p.Glu154Glyfs)

ENST00000313071.7:c.460dup

ENST00000313071.6:c.460dup

NM_005249.5:c.460dup

NC_000014.9:g.28767739dup

CM000676.2:g.28767739dup

NC_000014.8:g.29236945dup

CM000676.1:g.29236945dup

NC_000014.7:g.28306696dup

NG_009367.1:g.5659dup

Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PS2_Very Strong PM2_Supporting PS4 PVS1

Evidence Links 2

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Glu154Glyfs variant in FOXG1 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Glu154Glyfs variant in FOXG1 has been reported as a de novo occurrence (biological parentage confirmed) in at least 2 individuals with FOXG1 disorder (PMID 19806373, 28661489, Internal database-GeneDx) (PS2_VS). The p.Glu154Glyfs variant has also has been observed in at least 10 other individuals with FOXG1 disorder (PMID 19806373, 24836831, 26344814, 28851325, 29595814, 29655203, 29322350, 28661489) (PS4). The p.Glu154Glyfs variant in FOXG1 is absent from gnomAD (PM2_supporting). In summary, the p.Glu154Glyfs variant in FOXG1 is classified as Pathogenic for FOXG1 disorder based on the ACMG/AMP criteria (PVS1, PS2_VS, PS4, PM2_supporting).

PS2_Very Strong

The c.460dupG variant in FOXG1 has been reported as a confirmed de novo occurrence in at least 2 individuals with FOXG1-related disorders (PMID 19806373; 28661489; Internal database-GeneDx)

The c.460dupG variant in FOXG1 has been reported as a confirmed de novo occurrence in at least 2 individuals with FOXG1-related disorders (PMID 19806373; 28661489; Internal database-GeneDx) PubMed:19806373

PM2_Supporting

The c.460dupG variant in GENE is absent from gnomAD

PS4

"Met - strong The c.460dupG (p.Glu154Glyfs) has been observed in at least 10 other individuals with FOXG1-related disorders (PMID 19806373, 24836831, 26344814, 28851325, 29595814, 29655203, 29322350, 28661489)

PVS1

The c.460dupG variant in FOXG1 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism.

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.