NM_000346.4(SOX9):c.508C>T (p.Pro170Ser) AND Campomelic dysplasia with autosomal sex reversal

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 26, 2018
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:: RCV000853284.2

Allele description [Variation Report for NM_000346.4(SOX9):c.508C>T (p.Pro170Ser)]

NM_000346.4(SOX9):c.508C>T (p.Pro170Ser)

Gene:

SOX9:SRY-box transcription factor 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q24.3

Genomic location:

Preferred name:

NM_000346.4(SOX9):c.508C>T (p.Pro170Ser)

HGVS:

NC_000017.11:g.72122795C>T
NG_012490.1:g.6776C>T
NM_000346.4:c.508C>TMANE SELECT
NP_000337.1:p.Pro170Ser
NC_000017.10:g.70118936C>T
NM_000346.3:c.508C>T

Protein change:

P170S

Links:

dbSNP: rs866706988

NCBI 1000 Genomes Browser:

rs866706988

Molecular consequence:

NM_000346.4:c.508C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Campomelic dysplasia with autosomal sex reversal
Identifiers:: MedGen: C1842462

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000996119	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 26, 2018)	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

SCV000996119

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 26, 2018)

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	yes	1	not provided	not provided	1	not provided	clinical 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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV000996119.1

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

Description

This variant has been previously reported in an individual with multiple congenital anomalies (PMID: 26633542). Different missense variants affecting the same amino acid residue (p.Pro170Leu, p.Pro170Arg) have been reported in patients with acampomelic and campomelic dyplasia respectively (PMID: 19921652; 9002675). The p.Pro170Ser variant detected in this individual is absent from the ExAC and gnomAD population databases. It occurs at a highly conserved amino acid and is predicted by multiple in silico tools to be damaging to protein function. Based on the available evidence, the p.Pro170Ser variant in SOX9 is classified as a pathogenic change.

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

Last Updated: Nov 3, 2024

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