NM_000388.4(CASR):c.3047T>C (p.Leu1016Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 8, 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:: RCV001208896.6

Allele description [Variation Report for NM_000388.4(CASR):c.3047T>C (p.Leu1016Pro)]

NM_000388.4(CASR):c.3047T>C (p.Leu1016Pro)

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.3047T>C (p.Leu1016Pro)

HGVS:

NC_000003.12:g.122285001T>C
NG_009058.2:g.106334T>C
NM_000388.4:c.3047T>CMANE SELECT
NM_001178065.2:c.3077T>C
NP_000379.3:p.Leu1016Pro
NP_001171536.2:p.Leu1026Pro
NC_000003.11:g.122003848T>C
NG_009058.1:g.106319T>C
NM_000388.3:c.3047T>C

Protein change:

L1016P

Links:

dbSNP: rs755151413

NCBI 1000 Genomes Browser:

rs755151413

Molecular consequence:

NM_000388.4:c.3047T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.3077T>C - 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

Recent activity

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RecName: Full=Glycerol-3-phosphate dehydrogenase [NAD(+)], glycosomal
RecName: Full=Glycerol-3-phosphate dehydrogenase [NAD(+)], glycosomal
gi|74894367|sp|P90551.1|GPDA_LEIME

Protein
RecName: Full=Eukaryotic translation initiation factor 5A; Short=eIF-5A
RecName: Full=Eukaryotic translation initiation factor 5A; Short=eIF-5A
gi|410591639|sp|E9AXF0.1|IF5A_LEIMU

Protein
Danio rerio COPI coat complex subunit gamma 2 (copg2), mRNA
Danio rerio COPI coat complex subunit gamma 2 (copg2), mRNA
gi|18858452|ref|NM_130994.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001380308	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 8, 2023)	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

SCV001380308

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 8, 2023)

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, SCV001380308.5

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1016 of the CASR protein (p.Leu1016Pro). This variant is present in population databases (rs755151413, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 939485). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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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