NM_000516.7(GNAS):c.139+1G>C AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 17, 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:: RCV002557972.3

Allele description [Variation Report for NM_000516.7(GNAS):c.139+1G>C]

NM_000516.7(GNAS):c.139+1G>C

Gene:

GNAS:GNAS complex locus [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.32

Genomic location:

Preferred name:

NM_000516.7(GNAS):c.139+1G>C

HGVS:

NC_000020.11:g.58891866G>C
NG_016194.2:g.57127G>C
NM_000516.7:c.139+1G>CMANE SELECT
NM_001077488.5:c.139+1G>C
NM_001077489.4:c.139+1G>C
NM_001077490.3:c.*1-3746G>C
NM_001309840.2:c.-39+2513G>C
NM_001309842.2:c.139+1G>C
NM_001309861.2:c.-38-3746G>C
NM_001309883.1:c.*159-3746G>C
NM_001410912.1:c.44-3746G>C
NM_001410913.1:c.2069-3746G>C
NM_016592.5:c.*43-3746G>C
NM_080425.4:c.2069-3746G>C
NM_080426.4:c.139+1G>C
NC_000020.10:g.57466921G>C
NC_000020.10:g.57466921G>C
NM_001077488.3:c.139+1G>C

Links:

dbSNP: rs2089393181

NCBI 1000 Genomes Browser:

rs2089393181

Molecular consequence:

NM_001077490.3:c.*1-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001309840.2:c.-39+2513G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001309861.2:c.-38-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001309883.1:c.*159-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001410912.1:c.44-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001410913.1:c.2069-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_016592.5:c.*43-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_080425.4:c.2069-3746G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000516.7:c.139+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001077488.5:c.139+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001077489.4:c.139+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001309842.2:c.139+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_080426.4:c.139+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV003443843	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 17, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16199547, 11784876, 23281139, 23796510, 25802881, 20427508, 23884777, 31886927, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443843

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 17, 2022)

germline

clinical testing

PubMed (9)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia.

Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA, Kaplan FS.

N Engl J Med. 2002 Jan 10;346(2):99-106. Erratum in: N Engl J Med 2002 May 23;346(21):1678.

PubMed [citation]

PMID:: 11784876

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443843.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change affects a donor splice site in intron 1 of the GNAS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GNAS are known to be pathogenic (PMID: 11784876, 23281139, 23796510, 25802881). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with GNAS-related conditions (PMID: 20427508, 23884777, 31886927). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 873534). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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