NM_000785.4(CYP27B1):c.262del (p.Val88fs) AND Vitamin D-dependent rickets, type 1A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 15, 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:: RCV000001731.3

Allele description [Variation Report for NM_000785.4(CYP27B1):c.262del (p.Val88fs)]

NM_000785.4(CYP27B1):c.262del (p.Val88fs)

Gene:

CYP27B1:cytochrome P450 family 27 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q14.1

Genomic location:

Preferred name:

NM_000785.4(CYP27B1):c.262del (p.Val88fs)

HGVS:

NC_000012.12:g.57766131del
NG_007076.1:g.6063del
NM_000785.4:c.262delMANE SELECT
NP_000776.1:p.Val88fs
NC_000012.11:g.58159914del
NM_000785.3:c.262del
NM_000785.3:c.262delG

Protein change:

V88fs

Links:

OMIM: 609506.0007; dbSNP: rs387906260

NCBI 1000 Genomes Browser:

rs387906260

Molecular consequence:

NM_000785.4:c.262del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Vitamin D-dependent rickets, type 1A
Synonyms:: VITAMIN D HYDROXYLATION-DEFICIENT RICKETS, TYPE 1A; PDDR IA; PSEUDOVITAMIN D-DEFICIENCY RICKETS, TYPE IA
Identifiers:: MONDO: MONDO:0020723; MedGen: CN283242; OMIM: 264700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021887	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1998)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002600516	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000021887

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 1998)

germline

literature only

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

SCV002600516

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 15, 2022)

germline

clinical testing

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

Citation Link

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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families.

Wang JT, Lin CJ, Burridge SM, Fu GK, Labuda M, Portale AA, Miller WL.

Am J Hum Genet. 1998 Dec;63(6):1694-702.

PubMed [citation]

PMID:: 9837822
PMCID:: PMC1377641

Short- and long-term outcome of patients with pseudo-vitamin D deficiency rickets treated with calcitriol.

Edouard T, Alos N, Chabot G, Roughley P, Glorieux FH, Rauch F.

J Clin Endocrinol Metab. 2011 Jan;96(1):82-9. doi: 10.1210/jc.2010-1340. Epub 2010 Oct 6.

PubMed [citation]

PMID:: 20926527

Details of each submission

From OMIM, SCV000021887.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 9 of 10 alleles from French Canadian patients with vitamin D-dependent rickets type I (264700), Wang et al. (1998) identified a 1-bp deletion (958delG) in the CYP27B1 gene. Haplotype analysis was consistent with a founder effect. One other case, in a white patient from the US, was homozygous for the 958delG mutation.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002600516.1

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

Description

Variant summary: CYP27B1 c.262delG (p.Val88TrpfsX71) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.5e-05 in 142666 control chromosomes. c.262delG has been reported in the literature in multiple individuals affected with features of Vitamin D-Dependent Rickets, Type 1 (example, Edouard_2011). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as 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: Oct 13, 2024

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