NM_023067.4(FOXL2):c.840_850dup (p.Pro284fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 15, 2023
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:: RCV003553309.1

Allele description [Variation Report for NM_023067.4(FOXL2):c.840_850dup (p.Pro284fs)]

NM_023067.4(FOXL2):c.840_850dup (p.Pro284fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3q22.3

Genomic location:

Preferred name:

NM_023067.4(FOXL2):c.840_850dup (p.Pro284fs)

HGVS:

NC_000003.12:g.138945874_138945884dup
NG_012454.1:g.6258_6268dup
NG_029796.1:g.3641_3651dup
NM_023067.4:c.840_850dupMANE SELECT
NP_075555.1:p.Pro284fs
LRG_1295t1:c.840_850dup
LRG_1295:g.6258_6268dup
LRG_1295p1:p.Pro284fs
NC_000003.11:g.138664714_138664715insGTGCGGCCGGC
NC_000003.11:g.138664716_138664726dup

Protein change:

P284fs

Molecular consequence:

NM_023067.4:c.840_850dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004268382	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11468277, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004268382

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation.

De Baere E, Dixon MJ, Small KW, Jabs EW, Leroy BP, Devriendt K, Gillerot Y, Mortier G, Meire F, Van Maldergem L, Courtens W, Hjalgrim H, Huang S, Liebaers I, Van Regemorter N, Touraine P, Praphanphoj V, Verloes A, Udar N, Yellore V, Chalukya M, Yelchits S, et al.

Hum Mol Genet. 2001 Jul 15;10(15):1591-600.

PubMed [citation]

PMID:: 11468277

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004268382.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant disrupts a region of the FOXL2 protein in which other variant(s) (p.Pro307Hisfs*52) have been determined to be pathogenic (PMID: 11468277). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with FOXL2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Pro284Argfs*76) in the FOXL2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the FOXL2 protein.

#	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

Last Updated: Feb 20, 2024

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