Variant: NM_005249.5(FOXG1):c.430G>A (p.Glu144Lys)

Version: 1.0
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CA206112

211032 (ClinVar)

Gene: FOXG1 (HGNC:2290)

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

UUID: 927bf4da-dc44-4398-9fdb-e3384aff5a5a

Approved on: 2025-08-27

Published on: 2025-10-01

HGVS expressions

NM_005249.5:c.430G>A
NM_005249.5(FOXG1):c.430G>A (p.Glu144Lys)
NC_000014.9:g.28767709G>A
CM000676.2:g.28767709G>A
NC_000014.8:g.29236915G>A
CM000676.1:g.29236915G>A
NC_000014.7:g.28306666G>A
NG_009367.1:g.5629G>A
ENST00000706482.1:c.430G>A
ENST00000313071.7:c.430G>A
ENST00000313071.6:c.430G>A
NM_005249.4:c.430G>A

Uncertain Significance

• Met criteria codes: BP4 PS4_Supporting PM2_Supporting

• Not Met criteria codes: PS1 PM5 PM1 PVS1

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for FOXG1 Version 5.0.0

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Glu144Lys variant in FOXG1 is absent from gnomAD v4.1 (PM2_Supporting). The p.Glu144Lys variant has been observed in at least 2 individuals with neurodevelopmental phenotypes (internal databases - GeneDx and University of Chicago) (PS4_Supporting). The computational predictor REVEL gives a score of 0.112, which is below the threshold of 0.290, evidence that does not predict a damaging effect on FOXG1 function (BP4). In summary, the p.Glu144Lys variant in FOXG1 is classified as uncertain significance based on the ACMG/AMP criteria (PM2_Supporting, PS4_Supporting, BP4). (FOXG1 Specifications v.5.0.0; curation approved on 8/27/2025)

Met criteria codes

• BP4: The computational predictor REVEL gives a score of 0.112, which is below the threshold of 0.290, evidence that does not predict a damaging effect on FOXG1 function (BP4).
• PS4_Supporting: The p.Glu144Lys variant has been observed in at least 2 individuals with neurodevelopmental phenotypes (internal database - GeneDx and University of Chicago).
• PM2_Supporting: The p.Glu144Lys variant in FOXG1 is absent from gnomAD v4.1 (PM2_Supporting).

Not Met criteria codes

• PS1: 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
• PM1: 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