NM_001308093.3(GATA4):c.623T>A (p.Met208Lys) AND Renal cysts and diabetes syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 18, 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:: RCV001093712.1

Allele description [Variation Report for NM_001308093.3(GATA4):c.623T>A (p.Met208Lys)]

NM_001308093.3(GATA4):c.623T>A (p.Met208Lys)

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.623T>A (p.Met208Lys)

HGVS:

NC_000008.11:g.11748922T>A
NG_008177.2:g.77004T>A
NM_001308093.3:c.623T>AMANE SELECT
NM_001308094.2:c.2T>A
NM_001374273.1:c.2T>A
NM_001374274.1:c.2T>A
NM_002052.5:c.620T>A
NP_001295022.1:p.Met208Lys
NP_001295023.1:p.Met1Lys
NP_001361202.1:p.Met1Lys
NP_001361203.1:p.Met1Lys
NP_002043.2:p.Met207Lys
NC_000008.10:g.11606431T>A
NC_000008.10:g.11606431T>A
p.Met207Lys

Protein change:

M1K

Links:

dbSNP: rs140892695

NCBI 1000 Genomes Browser:

rs140892695

Molecular consequence:

NM_001308094.2:c.2T>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001374273.1:c.2T>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001374274.1:c.2T>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001308093.3:c.623T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001308094.2:c.2T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374273.1:c.2T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374274.1:c.2T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.620T>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Unknown function

Observations:

Condition(s)

Name:: Renal cysts and diabetes syndrome (RCAD)
Synonyms:: Maturity-onset diabetes of the young, type 5; MODY type 5; Hyperuricemic nephropathy, familial juvenile, atypical; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007669; MedGen: C0431693; Orphanet: 93111; OMIM: 137920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001190518	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 18, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001190518

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 18, 2020)

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
Gujarati/Hindu	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV001190518.2

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

Description

A heterozygous missense variation in exon 3 of the GATA4 gene that results in the amino acid substitution of Lysine for Methionine at codon 207 was detected. The observed variant c.620T>A (p.Met207Lys) has not been reported in the 1000 genomes and ExAC databases. Mutations in the GATA4 gene are associated with neonatal and childhood-onset diabetes (Shaw-Smith C. et al 2014). The in silico prediction of the variant is damaging by SIFT and MutationTaster2. The reference codon is conserved across mammals. In summary, the variant meets our criteria to be classed as a variant of unknown significance.

#	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		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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