Submissions for variant NM_001372066.1(TFAP2A):c.769A>G (p.Arg257Gly)

dbSNP: rs121909574

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Genetic Epidemiology, Research Centre for Medical Genetics	RCV000019530	SCV000223994	pathogenic	Branchiooculofacial syndrome		criteria provided, single submitter	research
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000019530	SCV000782345	pathogenic	Branchiooculofacial syndrome	2016-11-01	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000019530	SCV000993430	likely pathogenic	Branchiooculofacial syndrome	2019-10-23	criteria provided, single submitter	research	ACMG codes:PS2; PS4M; PM2; PP3
CeGaT Center for Human Genetics Tuebingen	RCV001090476	SCV001246047	pathogenic	not provided	2017-05-01	criteria provided, single submitter	clinical testing
Cytogenetics and Genomics Lab, Cyprus Institute Of Neurology and Genetics	RCV000019530	SCV001443809	pathogenic	Branchiooculofacial syndrome	2020-06-17	criteria provided, single submitter	research
Invitae	RCV001090476	SCV002247267	pathogenic	not provided	2021-10-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 C0"). ClinVar contains an entry for this variant (Variation ID: 17937). This missense change has been observed in individuals with branchiooculofacial syndrome (PMID: 18423521, 20358615, 20461149, 21539471, 25590586). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 255 of the TFAP2A protein (p.Arg255Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.
Revvity Omics, Revvity	RCV000019530	SCV003811520	likely pathogenic	Branchiooculofacial syndrome	2022-03-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001090476	SCV003836870	pathogenic	not provided	2023-03-01	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 25622170, 25590586, 21250552, 21539471, 20358615, 23578821, 2004100, 10767004, 7747785, 18423521, 34930662, 34324503)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000019530	SCV004045867	pathogenic	Branchiooculofacial syndrome	2023-08-16	criteria provided, single submitter	clinical testing
OMIM	RCV000019530	SCV000039827	pathogenic	Branchiooculofacial syndrome	2010-04-01	no assertion criteria provided	literature only