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NM_023067.4(FOXL2):c.644A>G (p.Tyr215Cys) AND FOXL2-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 11, 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:
RCV003392224.4

Allele description [Variation Report for NM_023067.4(FOXL2):c.644A>G (p.Tyr215Cys)]

NM_023067.4(FOXL2):c.644A>G (p.Tyr215Cys)

Gene:
FOXL2:forkhead box L2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q22.3
Genomic location:
Preferred name:
NM_023067.4(FOXL2):c.644A>G (p.Tyr215Cys)
HGVS:
  • NC_000003.12:g.138946079T>C
  • NG_012454.1:g.6062A>G
  • NG_029796.1:g.3846T>C
  • NM_023067.4:c.644A>GMANE SELECT
  • NP_075555.1:p.Tyr215Cys
  • LRG_1295t1:c.644A>G
  • LRG_1295:g.6062A>G
  • LRG_1295p1:p.Tyr215Cys
  • NC_000003.11:g.138664921T>C
  • NM_023067.3:c.644A>G
  • P58012:p.Tyr215Cys
  • p.[Tyr215Cys]
Protein change:
Y215C
Links:
UniProtKB: P58012#VAR_021203; dbSNP: rs1057516168
NCBI 1000 Genomes Browser:
rs1057516168
Molecular consequence:
  • NM_023067.4:c.644A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
FOXL2-related disorder
Synonyms:
FOXL2-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004119824PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Oct 11, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 PreventionGenetics, part of Exact Sciences, SCV004119824.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The FOXL2 c.644A>G variant is predicted to result in the amino acid substitution p.Tyr215Cys. This variant has been reported as segregating with disease in a five generation kindred with blepharophimosis-ptosis-epicanthus inversus syndrome (Kumar et al. 2004. PubMed ID: 15257268). This variant has also been reported in a sporadic case of BPES (Wang et al. 2022. PubMed ID: 36338666). A functional study using protein expression in cell culture found that the p.Tyr215Cys substitution causes protein aggregation (Dipietromaria et al. 2009. PubMed ID: 19515849). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Given all the evidence, we interpret this variant as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024