NM_001002295.2(GATA3):c.404del (p.Pro135fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 27, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001999809.7

Allele description [Variation Report for NM_001002295.2(GATA3):c.404del (p.Pro135fs)]

NM_001002295.2(GATA3):c.404del (p.Pro135fs)

Gene:

GATA3:GATA binding protein 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10p14

Genomic location:

Preferred name:

NM_001002295.2(GATA3):c.404del (p.Pro135fs)

HGVS:

NC_000010.11:g.8058467del
NG_015859.1:g.8764del
NM_001002295.2:c.404delMANE SELECT
NM_002051.3:c.404del
NP_001002295.1:p.Pro135fs
NP_002042.1:p.Pro135fs
NC_000010.10:g.8100425del
NC_000010.10:g.8100430del
NM_001002295.1:c.404del
NM_001002295.1:c.404delC

Protein change:

P135fs

Links:

dbSNP: rs772396478

NCBI 1000 Genomes Browser:

rs772396478

Molecular consequence:

NM_001002295.2:c.404del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002051.3:c.404del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002231833	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 22, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17210674, 14985365, 21242646, 28492532
SCV002770154	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 27, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002231833

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 22, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002770154

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 27, 2022)

germline

clinical testing

Citation Link

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome: insight into mechanisms of DNA binding by the GATA3 transcription factor.

Ali A, Christie PT, Grigorieva IV, Harding B, Van Esch H, Ahmed SF, Bitner-Glindzicz M, Blind E, Bloch C, Christin P, Clayton P, Gecz J, Gilbert-Dussardier B, Guillen-Navarro E, Hackett A, Halac I, Hendy GN, Lalloo F, Mache CJ, Mughal Z, Ong AC, Rinat C, et al.

Hum Mol Genet. 2007 Feb 1;16(3):265-75. Epub 2007 Jan 8.

PubMed [citation]

PMID:: 17210674

Characterization of GATA3 mutations in the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome.

Nesbit MA, Bowl MR, Harding B, Ali A, Ayala A, Crowe C, Dobbie A, Hampson G, Holdaway I, Levine MA, McWilliams R, Rigden S, Sampson J, Williams AJ, Thakker RV.

J Biol Chem. 2004 May 21;279(21):22624-34. Epub 2004 Feb 24.

PubMed [citation]

PMID:: 14985365

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231833.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with hypoparathyroidism, deafness, and renal dysplasia syndrome (PMID: 17210674). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro135Argfs*60) in the GATA3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATA3 are known to be pathogenic (PMID: 14985365, 21242646).

#	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

From GeneDx, SCV002770154.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17210674, 34136434)

#	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 8, 2024

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