NM_001372066.1(TFAP2A):c.687C>G (p.Tyr229Ter) AND Branchiooculofacial syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 12, 2020
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:: RCV002272588.2

Allele description [Variation Report for NM_001372066.1(TFAP2A):c.687C>G (p.Tyr229Ter)]

NM_001372066.1(TFAP2A):c.687C>G (p.Tyr229Ter)

Genes:

LOC121740638:BRD4-independent group 4 enhancer GRCh37_chr6:10403277-10404476 [Gene]
TFAP2A-AS2:TFAP2A antisense RNA 2 [Gene - OMIM - HGNC]
TFAP2A:transcription factor AP-2 alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_001372066.1(TFAP2A):c.687C>G (p.Tyr229Ter)

Other names:

NM_003220.2:c.681C>G

HGVS:

NC_000006.12:g.10404591G>C
NG_016151.1:g.19974C>G
NM_001032280.3:c.663C>G
NM_001042425.3:c.669C>G
NM_001372066.1:c.687C>GMANE SELECT
NP_001027451.1:p.Tyr221Ter
NP_001035890.1:p.Tyr223Ter
NP_001358995.1:p.Tyr229Ter
NC_000006.11:g.10404824G>C
NR_145448.1:n.90G>C

Protein change:

Y221*

Links:

dbSNP: rs2114014460

NCBI 1000 Genomes Browser:

rs2114014460

Molecular consequence:

NR_145448.1:n.90G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001032280.3:c.663C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001042425.3:c.669C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001372066.1:c.687C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Branchiooculofacial syndrome (BOFS)
Synonyms:: BOF SYNDROME; BOFS syndrome; Branchial clefts with characteristic facies growth retardation imperforate nasolacrimal duct and premature aging; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007235; MeSH: D019280; MedGen: C0376524; Orphanet: 1297; OMIM: 113620

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Homo sapiens transmembrane protein 201, mRNA (cDNA clone MGC:168911 IMAGE:902128...
Homo sapiens transmembrane protein 201, mRNA (cDNA clone MGC:168911 IMAGE:9021288), complete cds
gi|223460955|gb|BC137291.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002556396	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 12, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23578821, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002556396

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 12, 2020)

germline

clinical testing

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of TFAP2A mutations in Branchio-Oculo-Facial Syndrome indicates functional complexity within the AP-2α DNA-binding domain.

Li H, Sheridan R, Williams T.

Hum Mol Genet. 2013 Aug 15;22(16):3195-206. doi: 10.1093/hmg/ddt173. Epub 2013 Apr 10.

PubMed [citation]

PMID:: 23578821
PMCID:: PMC3723307

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 Genetics and Molecular Pathology, SA Pathology, SCV002556396.2

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

Description

The TFAP2A c.681C>G variant is classified as Likely Pathogenic (PVS1, PM2) The TFAP2A c.681C>G variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 227. This variant is absent from population databases (PM2). This variant is in exon 4 of 7 which encodes the DNA binding domain and which is a known mutational hotspot (PMID: 23578821).

#	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 13, 2024

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