NM_000784.4(CYP27A1):c.1140del (p.Phe380fs) AND Cholestanol storage disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 14, 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:: RCV002837679.3

Allele description [Variation Report for NM_000784.4(CYP27A1):c.1140del (p.Phe380fs)]

NM_000784.4(CYP27A1):c.1140del (p.Phe380fs)

Gene:

CYP27A1:cytochrome P450 family 27 subfamily A member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_000784.4(CYP27A1):c.1140del (p.Phe380fs)

HGVS:

NC_000002.12:g.218814143del
NG_007959.1:g.37395del
NM_000784.4:c.1140delMANE SELECT
NP_000775.1:p.Phe380fs
NC_000002.11:g.219678864del
NC_000002.11:g.219678866del

Protein change:

F380fs

Molecular consequence:

NM_000784.4:c.1140del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cholestanol storage disease (CTX)
Synonyms:: Cerebral cholesterinosis; CTX: Cerebrotendinous xanthomatosis; Cerebrotendinous Xanthomatosis
Identifiers:: MONDO: MONDO:0008948; MedGen: C0238052; Orphanet: 909; OMIM: 213700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003206147	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 14, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9392430, 10775536, 26937392, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003206147

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 14, 2022)

germline

clinical testing

PubMed (4)
[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

Four novel mutations of sterol 27-hydroxylase gene in Italian patients with cerebrotendinous xanthomatosis.

Garuti R, Croce MA, Tiozzo R, Dotti MT, Federico A, Bertolini S, Calandra S.

J Lipid Res. 1997 Nov;38(11):2322-34.

PubMed [citation]

PMID:: 9392430

Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis.

Verrips A, Hoefsloot LH, Steenbergen GC, Theelen JP, Wevers RA, Gabreëls FJ, van Engelen BG, van den Heuvel LP.

Brain. 2000 May;123 ( Pt 5):908-19.

PubMed [citation]

PMID:: 10775536

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003206147.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe380Leufs*28) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392).

#	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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