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]

Link to SEPIO compliant JSON-LD document

Variant: NM_005249.4(FOXG1):c.256delC (p.Gln86Argfs)

CA199433

189612 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3adb4e57-42ba-4d85-a85d-339b6d6df8fc

HGVS expressions

NM_005249.4:c.256delC

NM_005249.4:c.256del

NM_005249.4(FOXG1):c.256delC (p.Gln86Argfs)

ENST00000313071.7:c.256del

ENST00000313071.6:c.256del

NM_005249.5:c.256del

NC_000014.9:g.28767535del

CM000676.2:g.28767535del

NC_000014.8:g.29236741del

CM000676.1:g.29236741del

NC_000014.7:g.28306492del

NG_009367.1:g.5455del

Pathogenic

PM2_Supporting PVS1 PM6_Strong PS4_Moderate PP4

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.Gln86Argfs 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.Gln86Argfs variant in FOXG1 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with FOXG1 disorder (PMID 22739344, 2634418) (PM6_strong, PP4). This variant has been observed in at least 3 other individuals with FOXG1 disorder (PMID 22739344, 26344814) (PS4_moderate). The c.256delC variant in FOXG1 is absent from gnomAD (PM2_supporting). In summary, the p.Gln86Argfs variant in FOXG1 is classified as Pathogenic for FOXG1 disorder based on the ACMG/AMP criteria (PVS1, PM6_strong, PS4_moderate, PM2_supporting, PP4).

PM2_Supporting

The c.256delC variant in FOXG1 is absent from gnomAD

PVS1

The c.256delC 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.

PM6_Strong

The c.256delC variant in FOXG1 appears to be de novo in two patients with a clinical phenotype suggestive of a FOXG1-related disorder (PMID 22739344, 2634418)

The c.256delC variant in FOXG1 occurs in the unconfirmed de novo state in this individual with Rett-like syndrome. PubMed:22739344

The c.256delC variant in FOXG1 occurs in the unconfirmed de novo state in this individual with microcephaly, developmental delay, intellectual disability, hypotonia, hyperactivity, seizures, and motor disturbances PubMed:26344814

PS4_Moderate

The c.256delC (p.Gln86Argfs) variant has been observed in at least 3 other individuals with FOXG1-related disease (PMID 22739344, 26344814).

PP4

The patient is reported to have a clinical phenotype suggestive of a FOXG1-related disorder

Approved on: 2021-03-25

Published on: 2021-05-10

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.