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NM_000388.4(CASR):c.186-1G>T AND Nephrolithiasis/nephrocalcinosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 4, 2018
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:
RCV004018597.1

Allele description [Variation Report for NM_000388.4(CASR):c.186-1G>T]

NM_000388.4(CASR):c.186-1G>T

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.186-1G>T
HGVS:
  • NC_000003.12:g.122257080G>T
  • NG_009058.2:g.78413G>T
  • NM_000388.4:c.186-1G>TMANE SELECT
  • NM_001178065.2:c.186-1G>T
  • NC_000003.11:g.121975927G>T
  • NM_000388.3:c.186-1G>T
Note:
NCBI staff reviewed the sequence information reported in PubMed 11668634 Fig. 5 to determine the location of this allele on the current reference sequence.
Nucleotide change:
IVS2AS, G-T, -1
Links:
OMIM: 601199.0033; dbSNP: rs797044441
NCBI 1000 Genomes Browser:
rs797044441
Molecular consequence:
  • NM_000388.4:c.186-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001178065.2:c.186-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Nephrolithiasis/nephrocalcinosis
Identifiers:
MedGen: CN580796

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001174014Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 4, 2018) 		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

An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

D'Souza-Li L, Canaff L, Janicic N, Cole DE, Hendy GN.

Hum Mutat. 2001 Nov;18(5):411-21.

PubMed [citation]
PMID:
11668634

Details of each submission

From Ambry Genetics, SCV001174014.4

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

Description

The c.186-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 2 of the CASR gene. This mutation was detected in two family members with familial hypocalciuric hypercalcemia (FHH) and was not present in two unaffected individuals in the same family. Furthermore, functional studies performed at the RNA level showed that this mutation results in the skipping of exon 3 causing a frameshift that results in a premature stop codon leading to a predicted truncated protein of 153 amino acids (D'Souza-Li L et al. Hum. Mutat., 2001 Nov;18:411-21). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: Sep 29, 2024