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_005249.5(FOXG1):c.706A>G (p.Asn236Asp)

CA389475686

1878806 (ClinVar)

Gene: FOXG1 (HGNC:2290)

Condition: FOXG1 disorder (MONDO:0100040)

Inheritance Mode: Autosomal dominant inheritance

UUID: cce556e1-f5a0-4274-9858-77bc2aae1c45

Approved on: 2025-02-28

Published on: 2025-03-26

HGVS expressions

NM_005249.5(FOXG1):c.706A>G (p.Asn236Asp)

NM_005249.5:c.706A>G

NC_000014.9:g.28767985A>G

CM000676.2:g.28767985A>G

NC_000014.8:g.29237191A>G

CM000676.1:g.29237191A>G

NC_000014.7:g.28306942A>G

NG_009367.1:g.5905A>G

ENST00000706482.1:c.706A>G

ENST00000313071.7:c.706A>G

ENST00000313071.6:c.706A>G

NM_005249.4:c.706A>G

Likely Pathogenic

PS2 PP3 PM1 PM2_Supporting

Evidence Links 0

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 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The c.706A>G (p.Asn236Asp) variant in FOXG1 has been identified as a de novo occurrence with confirmed parental relationships in 1 individual with FOXG1 disorder (GeneDx: internal data) (PS2). The p.Asn236Asp variant occurs in the well-characterized forkhead functional domain (aa 181-275) of FOXG1 (PM1). The computational predictor REVEL gives a score of 0.955, which is above the threshold of 0.75, evidence that correlates with impact to FOXG1 function (PP3). The p.Asn236Asp variant in FOXG1 is absent from gnomAD v4.1 (PM2_Supporting). In summary, the p.Asn236Asp variant in FOXG1 is classified as Likely Pathogenic for FOXG1 syndrome based on the ACMG/AMP criteria (PS2, PM1, PP3, PM2_supporting) (FOXG1 specifications version 3.0; curation approved on 2/28/2025).

PS2

This variant has been identified as a de novo occurrence with confirmed parental relationships in 1 individual with FOXG1 disorder (GeneDx: internal data) (PS2).

PP3

The computational predictor REVEL gives a score of 0.955, which is above the threshold of 0.75, evidence that correlates with impact to FOXG1 function (PP3).

PM1

The p.Asn236Asp variant occurs in the well-characterized forkhead functional domain (aa 181-275) of FOXG1 (PM1).

PM2_Supporting

The p.Asn236Asp variant in FOXG1 is absent from gnomAD v4.1 (PM2_Supporting).

Curation History

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