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NM_000388.4(CASR):c.73C>T (p.Arg25Ter) AND Neonatal severe primary hyperparathyroidism

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 18, 2024
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:
RCV004586698.1

Allele description [Variation Report for NM_000388.4(CASR):c.73C>T (p.Arg25Ter)]

NM_000388.4(CASR):c.73C>T (p.Arg25Ter)

Gene:
CASR:calcium sensing receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q21.1
Genomic location:
Preferred name:
NM_000388.4(CASR):c.73C>T (p.Arg25Ter)
HGVS:
  • NC_000003.12:g.122254262C>T
  • NG_009058.1:g.75580C>T
  • NM_000388.4:c.73C>TMANE SELECT
  • NM_001178065.2:c.73C>T
  • NP_000379.3:p.Arg25Ter
  • NP_001171536.2:p.Arg25Ter
  • NC_000003.11:g.121973109C>T
  • NM_000388.3:c.73C>T
  • p.ARG25*
Protein change:
R25*
Links:
dbSNP: rs201633414
NCBI 1000 Genomes Browser:
rs201633414
Molecular consequence:
  • NM_000388.4:c.73C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001178065.2:c.73C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Neonatal severe primary hyperparathyroidism
Synonyms:
Neonatal severe hyperparathyroidism
Identifiers:
MONDO: MONDO:0009397; MedGen: C1832615; Orphanet: 417; OMIM: 239200

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005077214Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Apr 18, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites.

Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, Fratter C, Rust N, Christie PT, Turner JJ, Lemos MC, Bowl MR, Bouillon R, Brain C, Bridges N, Burren C, Connell JM, Jung H, Marks E, McCredie D, Mughal Z, Rodda C, et al.

Hum Mol Genet. 2012 Jun 15;21(12):2768-78. doi: 10.1093/hmg/dds105. Epub 2012 Mar 14.

PubMed [citation]
PMID:
22422767

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005077214.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: CASR c.73C>T (p.Arg25X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 8e-06 in 251326 control chromosomes. c.73C>T has been reported in the literature at a homozygous state in at-least one individual affected with Neonatal Severe Hyperparathyroidism and at a heterozygous state in one patient with familial hypocalciuric hypercalcaemia (example, Hannan_2012). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 22422767). ClinVar contains an entry for this variant (Variation ID: 372315). Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 8, 2024