NM_000515.5(GH1):c.291+6T>C AND Autosomal dominant isolated somatotropin deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 2017
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:: RCV000017338.27

Allele description [Variation Report for NM_000515.5(GH1):c.291+6T>C]

NM_000515.5(GH1):c.291+6T>C

Genes:

GH1:growth hormone 1 [Gene - OMIM - HGNC]
GH-LCR:growth hormone locus control region [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.3

Genomic location:

Preferred name:

NM_000515.5(GH1):c.291+6T>C

HGVS:

NC_000017.11:g.63918011A>G
NG_011676.1:g.5828T>C
NG_042788.1:g.919A>G
NM_000515.5:c.291+6T>CMANE SELECT
NM_022559.4:c.246+6T>C
NM_022560.4:c.172-87T>C
NC_000017.10:g.61995371A>G
NM_000515.4:c.291+6T>C

Note:

NCBI staff reviewed the sequence information reported in PubMed 8288694 Fig. 3 to determine the location of this allele on the current reference sequence.

Nucleotide change:

IVS3DS, T-C, +6

Links:

OMIM: 139250.0007; dbSNP: rs797044450

NCBI 1000 Genomes Browser:

rs797044450

Molecular consequence:

NM_000515.5:c.291+6T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_022559.4:c.246+6T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_022560.4:c.172-87T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Autosomal dominant isolated somatotropin deficiency (IGHD2)
Synonyms:: IGHD II; Isolated growth hormone deficiency type 2; Growth hormone deficiency, isolated autosomal dominant; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008250; MedGen: C0271567; Orphanet: 631; OMIM: 173100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037610	OMIM	no assertion criteria provided	Pathogenic (Jan 11, 2017)	germline	literature only	Phillips, J. A., III Personal Communication. 1983. Baltimore, Md.

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000037610

OMIM

no assertion criteria provided

Pathogenic
(Jan 11, 2017)

germline

literature only

Phillips, J. A., III Personal Communication. 1983. Baltimore, Md.

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

Details of each submission

From OMIM, SCV000037610.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

Description

Phillips and Cogan (1994) demonstrated a T-to-C transition in the sixth base of the donor splice site of intron 3 in a Turkish family with isolated growth hormone deficiency type II (IGHD2; 173100). The mutant GH gene was transfected into cultured mammalian cells, and the GH mRNA transcripts were analyzed by direct sequencing of their corresponding cDNAs. The mutation was found to inactivate the donor splice site of intron 3, resulting in alternative use of the donor splice site of intron 2 in conjunction with the acceptor site of intron 3. This alternative splicing pattern deleted or skipped exon 3, resulting in the loss of amino acids 32 to 71 from the corresponding mature GH protein products. All affected members of the family were heterozygous for the mutation and had low but measurable GH levels after stimulation. All responded well to treatment with exogenous GH. The mechanism of the dominant-negative effect is unknown; the mutant GH allele may inactivate the normal GH allele by formation of GH dimers or disruption of normal intracellular protein transport.

#	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: Apr 23, 2022

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