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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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003443843Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Apr 17, 2022)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024