NM_003108.4(SOX11):c.223C>G (p.His75Asp) AND Intellectual disability, autosomal dominant 27

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 9, 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:: RCV003150861.1

Allele description [Variation Report for NM_003108.4(SOX11):c.223C>G (p.His75Asp)]

NM_003108.4(SOX11):c.223C>G (p.His75Asp)

Gene:

SOX11:SRY-box transcription factor 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p25.2

Genomic location:

Preferred name:

NM_003108.4(SOX11):c.223C>G (p.His75Asp)

HGVS:

NC_000002.12:g.5692944C>G
NG_050751.1:g.5278C>G
NM_003108.4:c.223C>GMANE SELECT
NP_003099.1:p.His75Asp
NC_000002.11:g.5833076C>G

Protein change:

H75D

Molecular consequence:

NM_003108.4:c.223C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 27 (IDDMOH)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER WITH MICROCEPHALY AND WITH OR WITHOUT OCULAR MALFORMATIONS OR HYPOGONADOTROPIC HYPOGONADISM
Identifiers:: MONDO: MONDO:0014376; MedGen: C4014528; Orphanet: 1465; OMIM: 615866

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003839015	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 9, 2023)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 35341651, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003839015

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 9, 2023)

unknown

curation

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

Al-Jawahiri R, Foroutan A, Kerkhof J, McConkey H, Levy M, Haghshenas S, Rooney K, Turner J, Shears D, Holder M, Lefroy H, Castle B, Reis LM, Semina EV; University of Washington Centre for Mendelian Genomics (UW-CMG), Lachlan K, Chandler K, Wright T, Clayton-Smith J, Hug FP, Pitteloud N, Bartoloni L, et al.

Genet Med. 2022 Jun;24(6):1261-1273. doi: 10.1016/j.gim.2022.02.013. Epub 2022 Mar 24.

PubMed [citation]

PMID:: 35341651
PMCID:: PMC9245088

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 SIB Swiss Institute of Bioinformatics, SCV003839015.1

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

Description

This variant is interpreted as likely pathogenic for Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); De novo paternity and maternity not confirmed (PM6); Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (PM1); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3).

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

Last Updated: Aug 5, 2023

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