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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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000037610OMIM
no assertion criteria provided
Pathogenic
(Jan 11, 2017) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Details of each submission

From OMIM, SCV000037610.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature onlynot 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.

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

Last Updated: Apr 23, 2022