NM_000388.4(CASR):c.2332G>C (p.Gly778Arg) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 15, 2023
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:: RCV003230626.1

Allele description [Variation Report for NM_000388.4(CASR):c.2332G>C (p.Gly778Arg)]

NM_000388.4(CASR):c.2332G>C (p.Gly778Arg)

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.2332G>C (p.Gly778Arg)

HGVS:

NC_000003.12:g.122284286G>C
NG_009058.2:g.105619G>C
NM_000388.4:c.2332G>CMANE SELECT
NM_001178065.2:c.2362G>C
NP_000379.3:p.Gly778Arg
NP_001171536.2:p.Gly788Arg
NC_000003.11:g.122003133G>C
NG_009058.1:g.105604G>C
NM_000388.3:c.2332G>C

Protein change:

G778R

Links:

dbSNP: rs1479933693

NCBI 1000 Genomes Browser:

rs1479933693

Molecular consequence:

NM_000388.4:c.2332G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2362G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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Homo sapiens peptidylprolyl isomerase like 4 (PPIL4), mRNA
Homo sapiens peptidylprolyl isomerase like 4 (PPIL4), mRNA
gi|1653960533|ref|NM_139126.4|

Nucleotide
Spizixos semitorques voucher KIZ YXBL082 arylsulfatase I (ARSI) gene, partial cd...
Spizixos semitorques voucher KIZ YXBL082 arylsulfatase I (ARSI) gene, partial cds
gi|1341086242|gb|KY598284.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003928957	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31433865, 22422767, 32761341 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003928957

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 15, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expanding the spectrum of genetic variants in the calcium-sensing receptor (CASR) gene in hypercalcemic individuals.

Nissen PH, Rejnmark L.

Clin Endocrinol (Oxf). 2019 Nov;91(5):683-690. doi: 10.1111/cen.14078. Epub 2019 Sep 9.

PubMed [citation]

PMID:: 31433865

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

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003928957.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: CASR c.2332G>C (p.Gly778Arg) results in a non-conservative amino acid change located in the GPCR family 3, C-terminal domain (IPR017978) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251070 control chromosomes (gnomAD). c.2332G>C has been reported in the literature in individuals affected with Familial Hypocalciuric Hypercalcemia (e.g. Hannan_2012, Nissen_2019, Khairi_2020). 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. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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