NM_024514.5(CYP2R1):c.595C>T (p.Arg199Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 21, 2022
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:: RCV002541448.3

Allele description [Variation Report for NM_024514.5(CYP2R1):c.595C>T (p.Arg199Ter)]

NM_024514.5(CYP2R1):c.595C>T (p.Arg199Ter)

Genes:

CYP2R1:cytochrome P450 family 2 subfamily R member 1 [Gene - OMIM - HGNC]
PDE3B:phosphodiesterase 3B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.2

Genomic location:

Preferred name:

NM_024514.5(CYP2R1):c.595C>T (p.Arg199Ter)

HGVS:

NC_000011.10:g.14880541G>A
NG_007936.1:g.16665C>T
NM_001377214.1:c.250C>T
NM_001377215.1:c.250C>T
NM_001377216.1:c.250C>T
NM_001377217.1:c.433C>T
NM_001377227.1:c.250C>T
NM_024514.5:c.595C>TMANE SELECT
NP_001364143.1:p.Arg84Ter
NP_001364144.1:p.Arg84Ter
NP_001364145.1:p.Arg84Ter
NP_001364146.1:p.Arg145Ter
NP_001364156.1:p.Arg84Ter
NP_078790.2:p.Arg199Ter
NC_000011.9:g.14902087G>A

Protein change:

R145*

Links:

dbSNP: rs782285382

NCBI 1000 Genomes Browser:

rs782285382

Molecular consequence:

NM_001377214.1:c.250C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001377215.1:c.250C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001377216.1:c.250C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001377217.1:c.433C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001377227.1:c.250C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_024514.5:c.595C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002947235	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 21, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15128933, 22855339, 25942481, 33715104, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002947235

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 21, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase.

Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW.

Proc Natl Acad Sci U S A. 2004 May 18;101(20):7711-5. Epub 2004 May 5.

PubMed [citation]

PMID:: 15128933
PMCID:: PMC419671

Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency.

Al Mutair AN, Nasrat GH, Russell DW.

J Clin Endocrinol Metab. 2012 Oct;97(10):E2022-5. doi: 10.1210/jc.2012-1340. Epub 2012 Aug 1.

PubMed [citation]

PMID:: 22855339
PMCID:: PMC3462929

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002947235.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1332743). This variant has not been reported in the literature in individuals affected with CYP2R1-related conditions. This variant is present in population databases (rs782285382, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg199*) in the CYP2R1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP2R1 are known to be pathogenic (PMID: 15128933, 22855339, 25942481, 33715104).

#	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

ClinVar

Relating variation to medicine