NM_005249.5(FOXG1):c.339del (p.Ala114fs) AND Rett syndrome, congenital variant

Germline classification:: Likely pathogenic (1 submission)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003158017.2

Allele description [Variation Report for NM_005249.5(FOXG1):c.339del (p.Ala114fs)]

NM_005249.5(FOXG1):c.339del (p.Ala114fs)

Gene:

FOXG1:forkhead box G1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_005249.5(FOXG1):c.339del (p.Ala114fs)

HGVS:

NC_000014.9:g.28767618del
NG_009367.1:g.5538del
NM_005249.5:c.339delMANE SELECT
NP_005240.3:p.Ala114fs
NC_000014.8:g.29236824del
NM_005249.5:c.338delCMANE SELECT

Protein change:

A114fs

Molecular consequence:

NM_005249.5:c.339del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Rett syndrome, congenital variant
Identifiers:: MONDO: MONDO:0013270; MedGen: C3150705; Orphanet: 3095; OMIM: 613454

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003845982	Lifecell International Pvt. Ltd	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003845982

Lifecell International Pvt. Ltd

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Lifecell International Pvt. Ltd, SCV003845982.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	1	not provided	not provided	clinical testing	PubMed (1)

Description

A Heterozygous Frameshift variant c.338delC in Exon 1 of the FOXG1 gene that results in the amino acid substitution p.Ala114fs*78 was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Dec 2, 2023

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