NM_003106.4(SOX2):c.290T>C (p.Leu97Pro) AND Anophthalmia/microphthalmia-esophageal atresia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 8, 2008
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000013665.26

Allele description [Variation Report for NM_003106.4(SOX2):c.290T>C (p.Leu97Pro)]

NM_003106.4(SOX2):c.290T>C (p.Leu97Pro)

Genes:

LOC108281177:SOX2 5' regulatory region [Gene]
SOX2-OT:SOX2 overlapping transcript [Gene - OMIM - HGNC]
SOX2:SRY-box transcription factor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.33

Genomic location:

Preferred name:

NM_003106.4(SOX2):c.290T>C (p.Leu97Pro)

HGVS:

NC_000003.12:g.181712650T>C
NG_009080.1:g.5717T>C
NM_003106.4:c.290T>CMANE SELECT
NP_003097.1:p.Leu97Pro
LRG_719:g.5717T>C
NC_000003.11:g.181430438T>C

Protein change:

L97P; LEU97PRO

Links:

OMIM: 184429.0004; dbSNP: rs104893802

NCBI 1000 Genomes Browser:

rs104893802

Molecular consequence:

NM_003106.4:c.290T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Anophthalmia/microphthalmia-esophageal atresia syndrome (MCOPS3)
Synonyms:: Microphthalmia syndromic 3; Microphthalmia and esophageal atresia syndrome; Anophthalmia clinical with associated anomalies; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008799; MedGen: C1859773; Orphanet: 77298; OMIM: 206900

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AGOS_AFR003C [Eremothecium gossypii ATCC 10895]
AGOS_AFR003C [Eremothecium gossypii ATCC 10895]
Gene ID:4621788

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033912	OMIM	no assertion criteria provided	Pathogenic (Apr 8, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 15812812, 18385377

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033912

OMIM

no assertion criteria provided

Pathogenic
(Apr 8, 2008)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

SOX2 anophthalmia syndrome.

Ragge NK, Lorenz B, Schneider A, Bushby K, de Sanctis L, de Sanctis U, Salt A, Collin JR, Vivian AJ, Free SL, Thompson P, Williamson KA, Sisodiya SM, van Heyningen V, Fitzpatrick DR.

Am J Med Genet A. 2005 May 15;135(1):1-7; discussion 8.

PubMed [citation]

PMID:: 15812812

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.

Danno H, Michiue T, Hitachi K, Yukita A, Ishiura S, Asashima M.

Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5408-13. doi: 10.1073/pnas.0710954105. Epub 2008 Apr 2.

PubMed [citation]

PMID:: 18385377
PMCID:: PMC2291098

Details of each submission

From OMIM, SCV000033912.4

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

Description

In a 6-year-old girl with microphthalmia, sclerocornea, and coloboma of the right eye, sclerocornea and aphakia of the left eye, a mild learning disability, and seizures (MCOPS3; 206900), Ragge et al. (2005) identified heterozygosity for a de novo 290T-C transition in the SOX2 gene, resulting in a leu97-to-pro (L97P) substitution in the highly conserved HMG box of the protein. The mutation is predicted to cause loss of function.

In studies in Xenopus cells, Danno et al. (2008) demonstrated that the L97P mutation affected physical interaction between the SOX2 and OTX2 (600037) proteins and reduced induction of transcription of RAX (601881), another gene involved in eye development. Wildtype SOX2 potently bound to a conserved noncoding sequence 2 kb upstream of the RAX promoter, but L97P-mutant SOX2 did not.

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

Last Updated: Mar 26, 2023

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