NM_023067.4(FOXL2):c.663_692dup (p.Ala225_Ala234dup) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 19, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002524615.4

Allele description [Variation Report for NM_023067.4(FOXL2):c.663_692dup (p.Ala225_Ala234dup)]

NM_023067.4(FOXL2):c.663_692dup (p.Ala225_Ala234dup)

Gene:

FOXL2:forkhead box L2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3q22.3

Genomic location:

Preferred name:

NM_023067.4(FOXL2):c.663_692dup (p.Ala225_Ala234dup)

HGVS:

NC_000003.12:g.138946034_138946063dup
NG_012454.1:g.6081_6110dup
NG_029796.1:g.3801_3830dup
NM_023067.4:c.663_692dupMANE SELECT
NP_075555.1:p.Ala225_Ala234dup
LRG_1295t1:c.663_692dup
LRG_1295:g.6081_6110dup
LRG_1295p1:p.Ala225_Ala234dup
NC_000003.11:g.138664872_138664873insGCCGCAGCTGCTGCAGCCGCTGCGGCTGCC
NC_000003.11:g.138664876_138664905dup
NM_023067.3:c.663_692dup30
p.(Ala225_Ala234dup)
p.[Ala225_Ala234dup]

Links:

dbSNP: rs764243782

NCBI 1000 Genomes Browser:

rs764243782

Molecular consequence:

NM_023067.4:c.663_692dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003313949	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18642388, 23441113, 28492532
SCV003921710	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 28, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003313949

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV003921710

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 28, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome.

Beysen D, De Jaegere S, Amor D, Bouchard P, Christin-Maitre S, Fellous M, Touraine P, Grix AW, Hennekam R, Meire F, Oyen N, Wilson LC, Barel D, Clayton-Smith J, de Ravel T, Decock C, Delbeke P, Ensenauer R, Ebinger F, Gillessen-Kaesbach G, Hendriks Y, Kimonis V, et al.

Hum Mutat. 2008 Nov;29(11):E205-19. doi: 10.1002/humu.20819.

PubMed [citation]

PMID:: 18642388

Genetic analysis of the forkhead transcriptional factor 2 gene in three Chinese families with blepharophimosis syndrome.

Jiang H, Huang X, Su Z, Rao L, Wu S, Zhang T, Li K, Quan Q, Zhang K.

Mol Vis. 2013;19:418-23. Epub 2013 Feb 20.

PubMed [citation]

PMID:: 23441113
PMCID:: PMC3580973

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003313949.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (gnomAD no frequency). This variant, c.663_692dup, results in the insertion of 10 amino acid(s) of the FOXL2 protein (p.Ala225_Ala234dup), but otherwise preserves the integrity of the reading frame. This variant has been observed in individuals with FOXL2-related conditions (PMID: 18642388, 23441113). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 369923).

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

From GeneDx, SCV003921710.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Predicted to result in an in-frame addition of 10 amino acids in a poly-alanine tract; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23441113, 31048069, 27283035)

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine