NM_001363711.2(DUOX2):c.533G>T (p.Trp178Leu) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000493682.10

Allele description [Variation Report for NM_001363711.2(DUOX2):c.533G>T (p.Trp178Leu)]

NM_001363711.2(DUOX2):c.533G>T (p.Trp178Leu)

Gene:

DUOX2:dual oxidase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_001363711.2(DUOX2):c.533G>T (p.Trp178Leu)

HGVS:

NC_000015.10:g.45111566C>A
NG_009447.1:g.7596G>T
NG_016992.1:g.2242C>A
NM_001363711.2:c.533G>TMANE SELECT
NM_014080.5:c.533G>T
NP_001350640.1:p.Trp178Leu
NP_054799.4:p.Trp178Leu
NP_054799.4:p.Trp178Leu
NC_000015.9:g.45403764C>A
NM_014080.4:c.533G>T

Protein change:

W178L

Links:

dbSNP: rs190660925

NCBI 1000 Genomes Browser:

rs190660925

Molecular consequence:

NM_001363711.2:c.533G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014080.5:c.533G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000582243	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (May 11, 2017)	germline	clinical testing	Citation Link,
SCV004698739	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jan 1, 2024)	germline	clinical testing	Citation Link,
SCV005193779	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000582243

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(May 11, 2017)

germline

clinical testing

Citation Link,

SCV004698739

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Jan 1, 2024)

germline

clinical testing

Citation Link,

SCV005193779

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

not provided

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	not provided	not provided	clinical testing, not provided

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 GeneDx, SCV000582243.4

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

Description

The W178L variant in the DUOX2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. A variant at the same codon, W178C, has been reported in trans along with a splice site variant in an individual with transient congenital hypothyroidism. Parents were heterozygous carriers with normal thyroid function (Tan et al., 2016). The W178L variant is observed in 9/4,440 (0.2%) alleles from individuals of European (Non-Finnish) background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The W178L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret W178L as a variant of uncertain significance.

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

From CeGaT Center for Human Genetics Tuebingen, SCV004698739.8

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

Description

DUOX2: PM5

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

From Breakthrough Genomics, Breakthrough Genomics, SCV005193779.1

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

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

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine