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NM_000388.4(CASR):c.473G>A (p.Gly158Glu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 5, 2021
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:
RCV001067948.7

Allele description [Variation Report for NM_000388.4(CASR):c.473G>A (p.Gly158Glu)]

NM_000388.4(CASR):c.473G>A (p.Gly158Glu)

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.473G>A (p.Gly158Glu)
HGVS:
  • NC_000003.12:g.122257368G>A
  • NG_009058.2:g.78701G>A
  • NM_000388.4:c.473G>AMANE SELECT
  • NM_001178065.2:c.473G>A
  • NP_000379.3:p.Gly158Glu
  • NP_001171536.2:p.Gly158Glu
  • NC_000003.11:g.121976215G>A
  • NG_009058.1:g.78686G>A
  • NM_000388.3:c.473G>A
Protein change:
G158E
Links:
dbSNP: rs2074566747
NCBI 1000 Genomes Browser:
rs2074566747
Molecular consequence:
  • NM_000388.4:c.473G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178065.2:c.473G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypocalciuric hypercalcemia (FHH)
Synonyms:
Familial benign hypercalcemia
Identifiers:
MONDO: MONDO:0018458; MedGen: C1809471; OMIM: PS145980
Name:
Autosomal dominant hypocalcemia 1 (HYPOC1)
Synonyms:
HYPOCALCEMIA, FAMILIAL
Identifiers:
MONDO: MONDO:0011013; MedGen: C0342345; OMIM: 601198

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001233033Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 5, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001233033.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in an individual affected with familial hypocalciuric hypercalcaemia (FHH) (PMID: 22422767). ClinVar contains an entry for this variant (Variation ID: 861428). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 158 of the CASR protein (p.Gly158Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.

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

Last Updated: Mar 5, 2024