NM_181458.4(PAX3):c.667C>T (p.Arg223Ter) AND Waardenburg syndrome type 1

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Oct 1, 2021
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:: RCV001290145.4

Allele description [Variation Report for NM_181458.4(PAX3):c.667C>T (p.Arg223Ter)]

NM_181458.4(PAX3):c.667C>T (p.Arg223Ter)

Gene:

PAX3:paired box 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q36.1

Genomic location:

Preferred name:

NM_181458.4(PAX3):c.667C>T (p.Arg223Ter)

HGVS:

NC_000002.12:g.222232203G>A
NG_011632.1:g.71779C>T
NM_001127366.3:c.664C>T
NM_181457.4:c.667C>T
NM_181458.4:c.667C>TMANE SELECT
NM_181459.4:c.667C>T
NM_181460.4:c.667C>T
NM_181461.4:c.667C>T
NP_001120838.1:p.Arg222Ter
NP_852122.1:p.Arg223Ter
NP_852123.1:p.Arg223Ter
NP_852124.1:p.Arg223Ter
NP_852125.1:p.Arg223Ter
NP_852126.1:p.Arg223Ter
NC_000002.11:g.223096922G>A
NM_001127366.2:c.664C>T
NM_181457.3:c.667C>T
NM_181458.4:c.667C>T
NM_181459.3:c.667C>T

Protein change:

R222*

Links:

dbSNP: rs772241382

NCBI 1000 Genomes Browser:

rs772241382

Molecular consequence:

NM_001127366.3:c.664C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181457.4:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181458.4:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181459.4:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181460.4:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181461.4:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Waardenburg syndrome type 1 (WS1)
Synonyms:: WAARDENBURG SYNDROME WITH DYSTOPIA CANTHORUM; Waardenburg's syndrome type 1
Identifiers:: MONDO: MONDO:0008670; MedGen: C1847800; OMIM: 193500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001478198	Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2019)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001792239	Otorhinolaryngology Lab - LIM32, University of Sao Paulo School of Medicine Clinics Hospital	criteria provided, single submitter (ClinGen HL ACMG Specifications v1)	Pathogenic	germline	research	PubMed (2) [See all records that cite these PMIDs] 30311386, 34599368
SCV001976945	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 1, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34008892, 25741868
SCV004171872	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	3	not provided	not provided	3	yes	clinical testing, research
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss.

Oza AM, DiStefano MT, Hemphill SE, Cushman BJ, Grant AR, Siegert RK, Shen J, Chapin A, Boczek NJ, Schimmenti LA, Murry JB, Hasadsri L, Nara K, Kenna M, Booth KT, Azaiez H, Griffith A, Avraham KB, Kremer H, Rehm HL, Amr SS, Abou Tayoun AN; et al.

Hum Mutat. 2018 Nov;39(11):1593-1613. doi: 10.1002/humu.23630.

PubMed [citation]

PMID:: 30311386
PMCID:: PMC6188673

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss.

Batissoco AC, Pedroso-Campos V, Pardono E, Sampaio-Silva J, Sonoda CY, Vieira-Silva GA, da Silva de Oliveira Longati EU, Mariano D, Hoshino ACH, Tsuji RK, Jesus-Santos R, Abath-Neto O, Bento RF, Oiticica J, Lezirovitz K.

Hum Genet. 2022 Apr;141(3-4):519-538. doi: 10.1007/s00439-021-02372-2. Epub 2021 Oct 1.

PubMed [citation]

PMID:: 34599368

See all PubMed Citations (4)

Details of each submission

From Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, SCV001478198.1

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

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

From Otorhinolaryngology Lab - LIM32, University of Sao Paulo School of Medicine Clinics Hospital, SCV001792239.1

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

Description

Familial case: proband with bilateral profound sensorineural hearing loss, Telecanthus, nasal wings hypoplasia and hyperplasia of nasal root, and synophris, Blue hypoplastic irides and white hair forelock. Paternal grandmother and paternal aunt are also carriers of this variant and affected by only facial dysmorphisms

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

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV001976945.1

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

Description

PVS1, PM1, PM2, PP3, PP4, PP5

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004171872.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	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: Apr 15, 2024

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