NM_000516.7(GNAS):c.34C>T (p.Gln12Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 13, 2024
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:: RCV003556238.3

Allele description [Variation Report for NM_000516.7(GNAS):c.34C>T (p.Gln12Ter)]

NM_000516.7(GNAS):c.34C>T (p.Gln12Ter)

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.34C>T (p.Gln12Ter)

HGVS:

NC_000020.11:g.58891760C>T
NG_016194.2:g.57021C>T
NM_000516.7:c.34C>TMANE SELECT
NM_001077488.5:c.34C>T
NM_001077489.4:c.34C>T
NM_001077490.3:c.*1-3852C>T
NM_001309840.2:c.-39+2407C>T
NM_001309842.2:c.34C>T
NM_001309861.2:c.-38-3852C>T
NM_001309883.1:c.*159-3852C>T
NM_016592.5:c.*43-3852C>T
NM_080425.4:c.2069-3852C>T
NM_080426.4:c.34C>T
NP_000507.1:p.Gln12Ter
NP_001070956.1:p.Gln12Ter
NP_001070957.1:p.Gln12Ter
NP_001296771.1:p.Gln12Ter
NP_536351.1:p.Gln12Ter
NC_000020.10:g.57466815C>T
NM_000516.4:c.34C>T
NM_000516.5:c.34C>T

Protein change:

Q12*

Links:

dbSNP: rs797045046

NCBI 1000 Genomes Browser:

rs797045046

Molecular consequence:

NM_001077490.3:c.*1-3852C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001309840.2:c.-39+2407C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001309861.2:c.-38-3852C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001309883.1:c.*159-3852C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_016592.5:c.*43-3852C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_080425.4:c.2069-3852C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000516.7:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001077488.5:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001077489.4:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001309842.2:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_080426.4:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004298102	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 16, 2023)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 11092390, 21525160, 23533243, 27703483, 29059381, 31886927, 33144682, 11784876, 23281139, 23796510, 25802881, 28492532
SCV005078106	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 13, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298102

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 16, 2023)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

SCV005078106

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 13, 2024)

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

Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification.

Eddy MC, Jan De Beur SM, Yandow SM, McAlister WH, Shore EM, Kaplan FS, Whyte MP, Levine MA.

J Bone Miner Res. 2000 Nov;15(11):2074-83.

PubMed [citation]

PMID:: 11092390

Increased prevalence of carpal tunnel syndrome in albright hereditary osteodystrophy.

Joseph AW, Shoemaker AH, Germain-Lee EL.

J Clin Endocrinol Metab. 2011 Jul;96(7):2065-73. doi: 10.1210/jc.2011-0013. Epub 2011 Apr 27.

PubMed [citation]

PMID:: 21525160
PMCID:: PMC3135204

See all PubMed Citations (12)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298102.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 209158). This premature translational stop signal has been observed in individual(s) with GNAS-related conditions (PMID: 11092390, 21525160, 23533243, 27703483, 29059381, 31886927, 33144682). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln12*) in the GNAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNAS are known to be pathogenic (PMID: 11784876, 23281139, 23796510, 25802881).

#	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, SCV005078106.1

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

Description

Nonsense 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: 25525159, 21525160, 11092390, 23533243, 27703483, 31886927, 33144682, 29059381)

#	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: Nov 3, 2024

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