NM_001372066.1(TFAP2A):c.743C>A (p.Ala248Glu) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 31, 2022
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:: RCV003037138.2

Allele description [Variation Report for NM_001372066.1(TFAP2A):c.743C>A (p.Ala248Glu)]

NM_001372066.1(TFAP2A):c.743C>A (p.Ala248Glu)

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.743C>A (p.Ala248Glu)

HGVS:

NC_000006.12:g.10404535G>T
NG_016151.1:g.20030C>A
NG_075700.2:g.1592G>T
NM_001032280.3:c.719C>A
NM_001042425.3:c.725C>A
NM_001372066.1:c.743C>AMANE SELECT
NP_001027451.1:p.Ala240Glu
NP_001035890.1:p.Ala242Glu
NP_001358995.1:p.Ala248Glu
NC_000006.11:g.10404768G>T
NG_075700.1:g.480G>T
NR_145448.1:n.34G>T

Protein change:

A240E

Molecular consequence:

NM_001032280.3:c.719C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042425.3:c.725C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372066.1:c.743C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_145448.1:n.34G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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LOC108799904 [Nanorana parkeri]
LOC108799904 [Nanorana parkeri]
Gene ID:108799904

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439397	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 31, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23578821, 21204207, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439397

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 31, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	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

Genotype-phenotype analysis of the branchio-oculo-facial syndrome.

Milunsky JM, Maher TM, Zhao G, Wang Z, Mulliken JB, Chitayat D, Clemens M, Stalker HJ, Bauer M, Burch M, Chénier S, Cunningham ML, Drack AV, Janssens S, Karlea A, Klatt R, Kini U, Klein O, Lachmeijer AM, Megarbane A, Mendelsohn NJ, Meschino WS, et al.

Am J Med Genet A. 2011 Jan;155A(1):22-32. doi: 10.1002/ajmg.a.33783.

PubMed [citation]

PMID:: 21204207

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003439397.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects TFAP2A function (PMID: 23578821). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This missense change has been observed in individuals with clinical features of branchiooculofacial syndrome (PMID: 21204207; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 246 of the TFAP2A protein (p.Ala246Glu).

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

Last Updated: Feb 14, 2024

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