NM_000388.4(CASR):c.2250C>A (p.Ser750Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 23, 2019
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:: RCV001216855.7

Allele description [Variation Report for NM_000388.4(CASR):c.2250C>A (p.Ser750Arg)]

NM_000388.4(CASR):c.2250C>A (p.Ser750Arg)

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.2250C>A (p.Ser750Arg)

HGVS:

NC_000003.12:g.122284204C>A
NG_009058.2:g.105537C>A
NM_000388.4:c.2250C>AMANE SELECT
NM_001178065.2:c.2280C>A
NP_000379.3:p.Ser750Arg
NP_001171536.2:p.Ser760Arg
NC_000003.11:g.122003051C>A
NG_009058.1:g.105522C>A
NM_000388.3:c.2250C>A

Protein change:

S750R

Links:

dbSNP: rs1559968879

NCBI 1000 Genomes Browser:

rs1559968879

Molecular consequence:

NM_000388.4:c.2250C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2280C>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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AGENCOURT_15183081 NICHD_XGC_Emb4 Xenopus laevis cDNA clone IMAGE:5515934 5', mRNA sequence
gi|33645961|gnl|dbEST|19539374|gb|C 82.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001388672	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 23, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001388672

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 23, 2019)

germline

clinical testing

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

Help

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001388672.5

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

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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 750 of the CASR protein (p.Ser750Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine.

#	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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