Variant: NM_005249.5(FOXG1):c.382G>T (p.Gly128Cys)

CA258396564

673188 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

UUID: 6275fddc-84fb-43e4-9e1f-efdbc2b1bf3d

Approved on: 2024-08-30

Published on: 2024-12-13

HGVS expressions

NM_005249.5:c.382G>T
NM_005249.5(FOXG1):c.382G>T (p.Gly128Cys)
NC_000014.9:g.28767661G>T
CM000676.2:g.28767661G>T
NC_000014.8:g.29236867G>T
CM000676.1:g.29236867G>T
NC_000014.7:g.28306618G>T
NG_009367.1:g.5581G>T
ENST00000706482.1:c.382G>T
ENST00000313071.7:c.382G>T
ENST00000313071.6:c.382G>T
NM_005249.4:c.382G>T

Likely Benign

• Met criteria codes: BS2 BP5

• Not Met criteria codes: PM2 BA1 BS1 BP4

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

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Gly128Cys variant is observed in at least 2 unaffected individuals (internal databases - GeneDx and Invitae) (BS2). The p.Gly128Cys variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5). The highest population minor allele frequency of the p.Gly128Cys variant in FOXG1 in gnomAD v4.1 is 0.00001400 in African/African American population (not sufficient to meet BS1 criteria). In summary, the p.Gly128Cys variant variant in FOXG1 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP5). (FOXG1 specification v.3; approved on 8/30/2024)

Met criteria codes

• BS2: The p.Gly128Cys variant is observed in at least 2 unaffected individuals (internal databases - GeneDx and Invitae) (BS2).
• BP5: The p.Gly128Cys variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5).

Not Met criteria codes

• PM2: The highest population minor allele frequency of the p.Gly128Cys variant in FOXG1 in gnomAD v4.1 is 0.00001400 in African/African American population (not sufficient to meet PM2_supporting criteria).
• BA1: The highest population minor allele frequency of the p.Gly128Cys variant in FOXG1 in gnomAD v4.1 is 0.00001400 in African/African American population (not sufficient to meet BA1 criteria).
• BS1: The highest population minor allele frequency of the p.Gly128Cys variant in FOXG1 in gnomAD v4.1 is 0.00001400 in African/African American population (not sufficient to meet BS1 criteria).
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline