NM_000516.7(GNAS):c.10dup (p.Leu4fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 22, 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:: RCV002880682.3

Allele description [Variation Report for NM_000516.7(GNAS):c.10dup (p.Leu4fs)]

NM_000516.7(GNAS):c.10dup (p.Leu4fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

20q13.32

Genomic location:

Preferred name:

NM_000516.7(GNAS):c.10dup (p.Leu4fs)

HGVS:

NC_000020.11:g.58891736dup
NG_016194.2:g.56997dup
NM_000516.7:c.10dupMANE SELECT
NM_001077488.5:c.10dup
NM_001077489.4:c.10dup
NM_001077490.3:c.*1-3876dup
NM_001309840.2:c.-39+2383dup
NM_001309842.2:c.10dup
NM_001309861.2:c.-38-3876dup
NM_001309883.1:c.*159-3876dup
NM_016592.5:c.*43-3876dup
NM_080425.4:c.2069-3876dup
NM_080426.4:c.10dup
NP_000507.1:p.Leu4fs
NP_001070956.1:p.Leu4fs
NP_001070957.1:p.Leu4fs
NP_001296771.1:p.Leu4fs
NP_536351.1:p.Leu4fs
NC_000020.10:g.57466789_57466790insC
NC_000020.10:g.57466791dup

Protein change:

L4fs

Molecular consequence:

NM_000516.7:c.10dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077488.5:c.10dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077489.4:c.10dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001309842.2:c.10dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080426.4:c.10dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077490.3:c.*1-3876dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001309840.2:c.-39+2383dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001309861.2:c.-38-3876dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001309883.1:c.*159-3876dup - intron variant - [Sequence Ontology: SO:0001627]
NM_016592.5:c.*43-3876dup - intron variant - [Sequence Ontology: SO:0001627]
NM_080425.4:c.2069-3876dup - intron variant - [Sequence Ontology: SO:0001627]

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
SCV003234802	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11784876, 23281139, 23796510, 25802881, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003234802

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 22, 2022)

germline

clinical testing

PubMed (5)
[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

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

Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations.

Elli FM, deSanctis L, Ceoloni B, Barbieri AM, Bordogna P, Beck-Peccoz P, Spada A, Mantovani G.

Hum Mutat. 2013 Mar;34(3):411-6. doi: 10.1002/humu.22265. Epub 2013 Jan 18.

PubMed [citation]

PMID:: 23281139

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003234802.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Leu4Profs*5) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GNAS-related conditions. 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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