Variant: NM_005249.5(FOXG1):c.685A>C (p.Ile229Leu)

CA16621657

425040 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

UUID: 8f7a9d2e-ff03-406d-88b5-34d80f6d48d0

Approved on: 2022-02-18

Published on: 2022-06-30

HGVS expressions

NM_005249.5:c.685A>C
NM_005249.5(FOXG1):c.685A>C (p.Ile229Leu)
NC_000014.9:g.28767964A>C
CM000676.2:g.28767964A>C
NC_000014.8:g.29237170A>C
CM000676.1:g.29237170A>C
NC_000014.7:g.28306921A>C
NG_009367.1:g.5884A>C
ENST00000313071.7:c.685A>C
ENST00000313071.6:c.685A>C
NM_005249.4:c.685A>C

Likely Pathogenic

• Met criteria codes: PM2_Supporting PP3 PM6 PM1

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Ile229Leu variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PMID 18571142, 28661489) (PM1). The p.Ile229Leu variant in FOXG1 occurs in the de novo state (biological parentage unconfirmed) in an individual with intellectual disability and seizures (Genetic Services Laboratory, University of Chicago internal data)(PM6). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance (PP3). The p.Ile229Leu variant in FOXG1 is absent in gnomAD (PM2_supporting). In summary, the p.Ile229Leu variant in FOXG1 is classified as likely pathogenic for FOXG1 disorder based on the ACMG/AMP criteria (PM1, PM6, PP3, PM2_supporting).

Met criteria codes

• PM2_Supporting: The p.Ile229Leu variant in FOXG1 is absent in gnomAD.
• PP3: Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance.
• PM6: The p.Ile229Leu variant in FOXG1 occurs in the de novo state (biological parentage unconfirmed) in an individual with intellectual disability and seizures (Genetic Services Laboratory, University of Chicago internal data).
• PM1: The p.Ile229Leu variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (Forkhead: aa 181-275; PMID 18571142, 28661489).