NM_001308093.3(GATA4):c.851G>A (p.Arg284His) AND Atrioventricular septal defect 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 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:: RCV002546407.3

Allele description [Variation Report for NM_001308093.3(GATA4):c.851G>A (p.Arg284His)]

NM_001308093.3(GATA4):c.851G>A (p.Arg284His)

Gene:

GATA4:GATA binding protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.1

Genomic location:

Preferred name:

NM_001308093.3(GATA4):c.851G>A (p.Arg284His)

HGVS:

NC_000008.11:g.11750175G>A
NG_008177.2:g.78257G>A
NM_001308093.3:c.851G>AMANE SELECT
NM_001308094.2:c.230G>A
NM_001374273.1:c.230G>A
NM_001374274.1:c.165+1090G>A
NM_002052.4:c.848G>A
NM_002052.5:c.848G>A
NP_001295022.1:p.Arg284His
NP_001295023.1:p.Arg77His
NP_001361202.1:p.Arg77His
NP_002043.2:p.Arg283His
NC_000008.10:g.11607684G>A
NM_002052.3:c.848G>A

Protein change:

R283H

Links:

dbSNP: rs180765750

NCBI 1000 Genomes Browser:

rs180765750

Molecular consequence:

NM_001374274.1:c.165+1090G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001308093.3:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001308094.2:c.230G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374273.1:c.230G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.848G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrioventricular septal defect 4 (AVSD4)
Identifiers:: MONDO: MONDO:0013747; MedGen: C3280781; OMIM: 614430

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003233229	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15863664, 23138528, 23696316, 32719394, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003233229

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2022)

germline

clinical testing

PubMed (5)
[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

GATA4 zinc finger mutations as a molecular rationale for septation defects of the human heart.

Reamon-Buettner SM, Borlak J.

J Med Genet. 2005 May;42(5):e32. No abstract available.

PubMed [citation]

PMID:: 15863664
PMCID:: PMC1736044

Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia.

Yu L, Wynn J, Cheung YH, Shen Y, Mychaliska GB, Crombleholme TM, Azarow KS, Lim FY, Chung DH, Potoka D, Warner BW, Bucher B, Stolar C, Aspelund G, Arkovitz MS, Chung WK.

Hum Genet. 2013 Mar;132(3):285-92. doi: 10.1007/s00439-012-1249-0. Epub 2012 Nov 9.

PubMed [citation]

PMID:: 23138528
PMCID:: PMC3570587

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003233229.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GATA4 protein function. ClinVar contains an entry for this variant (Variation ID: 1029405). This missense change has been observed in individual(s) with congenital diaphragmatic hernia and/or syndromic structural heart defects (PMID: 15863664, 23138528, 23696316, 32719394). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 283 of the GATA4 protein (p.Arg283His).

#	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: Nov 24, 2024

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