NM_000529.2(MC2R):c.652_653insA (p.Ala218fs) AND Glucocorticoid deficiency 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2008
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000003419.4

Allele description [Variation Report for NM_000529.2(MC2R):c.652_653insA (p.Ala218fs)]

NM_000529.2(MC2R):c.652_653insA (p.Ala218fs)

Gene:

MC2R:melanocortin 2 receptor [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

18p11.21

Genomic location:

Preferred name:

NM_000529.2(MC2R):c.652_653insA (p.Ala218fs)

HGVS:

NC_000018.10:g.13884866_13884867insT
NG_011819.1:g.35670_35671insA
NM_000529.2:c.652_653insAMANE SELECT
NM_001291911.1:c.652_653insA
NP_000520.1:p.Ala218fs
NP_001278840.1:p.Ala218fs
NC_000018.9:g.13884865_13884866insT

Protein change:

A218fs

Links:

OMIM: 607397.0006

Molecular consequence:

NM_000529.2:c.652_653insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001291911.1:c.652_653insA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Glucocorticoid deficiency 1 (GCCD1)
Synonyms:: FAMILIAL GLUCOCORTICOID DEFICIENCY 1; ACTH resistance; Adrenal unresponsiveness to acth; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024536; MedGen: C4049650; Orphanet: 361; OMIM: 202200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023577	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8636348, 18492762

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023577

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2008)

germline

literature only

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency.

Naville D, Barjhoux L, Jaillard C, Faury D, Despert F, Esteva B, Durand P, Saez JM, Begeot M.

J Clin Endocrinol Metab. 1996 Apr;81(4):1442-8.

PubMed [citation]

PMID:: 8636348

A novel adrenocorticotropin receptor mutation alters its structure and function, causing familial glucocorticoid deficiency.

Artigas RA, Gonzalez A, Riquelme E, Carvajal CA, Cattani A, Martínez-Aguayo A, Kalergis AM, Pérez-Acle T, Fardella CE.

J Clin Endocrinol Metab. 2008 Aug;93(8):3097-105. doi: 10.1210/jc.2008-0048. Epub 2008 May 20.

PubMed [citation]

PMID:: 18492762

Details of each submission

From OMIM, SCV000023577.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Naville et al. (1996) reported a patient with glucocorticoid deficiency (GCCD1; 202200) who was compound heterozygous for an A insertion that changed the reading frame after glycine-217 and led to a stop codon within the third extracellular loop, and a G-to-T transition that results in a cysteine-to-phenylalanine conversion at position 251 in the third extracellular loop (C251F; 607397.0007).

In a male with familial glucocorticoid deficiency, Artigas et al. (2008) detected compound heterozygosity for an adenine insertion (insA1347) and a novel missense mutation (A126S; 607397.0010) in the MC2R gene. The insertion resulted in frameshift (G217fs) and a premature stop codon codifying an aberrant receptor of 247 residues (27.2 kD). The family history showed nonconsanguineous healthy parents, 3 healthy sibs, and 1 brother with glucocorticoid deficiency.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 15, 2022

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