NM_003106.4(SOX2):c.869G>C (p.Ser290Thr) AND Anophthalmia/microphthalmia-esophageal atresia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 2022
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:: RCV002570759.3

Allele description [Variation Report for NM_003106.4(SOX2):c.869G>C (p.Ser290Thr)]

NM_003106.4(SOX2):c.869G>C (p.Ser290Thr)

Genes:

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.869G>C (p.Ser290Thr)

HGVS:

NC_000003.12:g.181713229G>C
NG_009080.1:g.6296G>C
NM_003106.4:c.869G>CMANE SELECT
NP_003097.1:p.Ser290Thr
LRG_719:g.6296G>C
NC_000003.11:g.181431017G>C
NM_003106.3:c.869G>C

Protein change:

S290T

Links:

dbSNP: rs779686992

NCBI 1000 Genomes Browser:

rs779686992

Molecular consequence:

NM_003106.4:c.869G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003262398	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2022)	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

SCV003262398

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2022)

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003262398.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1201570). This variant has not been reported in the literature in individuals affected with SOX2-related conditions. This variant is present in population databases (rs779686992, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 290 of the SOX2 protein (p.Ser290Thr).

#	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: Sep 29, 2024

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