NM_000388.4(CASR):c.679C>T (p.Arg227Ter) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Dec 11, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000657571.3

Allele description [Variation Report for NM_000388.4(CASR):c.679C>T (p.Arg227Ter)]

NM_000388.4(CASR):c.679C>T (p.Arg227Ter)

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.679C>T (p.Arg227Ter)
HGVS:
  • NC_000003.12:g.122261714C>T
  • NG_009058.1:g.83032C>T
  • NM_000388.4:c.679C>TMANE SELECT
  • NM_001178065.2:c.679C>T
  • NP_000379.3:p.Arg227Ter
  • NP_001171536.2:p.Arg227Ter
  • NC_000003.11:g.121980561C>T
  • NM_000388.3:c.679C>T
Protein change:
R227*
Links:
dbSNP: rs1085307984
NCBI 1000 Genomes Browser:
rs1085307984
Molecular consequence:
  • NM_000388.4:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001178065.2:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000779308GeneDxcriteria provided, single submitter
Pathogenic
(May 6, 2018)
germlineclinical testing

Citation Link,

SCV001143444Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Oct 9, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001449731Clinical Genetics Karolinska University Hospital,Karolinska University Hospitalcriteria provided, single submitter
Likely pathogenic
(Dec 11, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Neonatal severe hyperparathyroidism: further clinical and molecular delineation.

Al-Khalaf FA, Ismail A, Soliman AT, Cole DE, Ben-Omran T.

Eur J Pediatr. 2011 May;170(5):625-31. doi: 10.1007/s00431-010-1335-z. Epub 2010 Oct 23.

PubMed [citation]
PMID:
20972686

Heterozygous inactivating CaSR mutations causing neonatal hyperparathyroidism: function, inheritance and phenotype.

Glaudo M, Letz S, Quinkler M, Bogner U, Elbelt U, Strasburger CJ, Schnabel D, Lankes E, Scheel S, Feldkamp J, Haag C, Schulze E, Frank-Raue K, Raue F, Mayr B, Schöfl C.

Eur J Endocrinol. 2016 Nov;175(5):421-31. doi: 10.1530/EJE-16-0223.

PubMed [citation]
PMID:
27666534
See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000779308.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R227X nonsense variant in the CASR gene has been reported previously in association with familial hypocalciuric hypercalcemia, as well as with neonatal severe primary hyperparathyroidism when observed in the homozygous state (Vargas-Poussou et al., 2016; Al-Khalaf et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.

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

From Athena Diagnostics Inc, SCV001143444.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. Damaging to protein function(s) relevant to disease mechanism.

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

From Clinical Genetics Karolinska University Hospital,Karolinska University Hospital, SCV001449731.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Apr 12, 2021

Support Center