NM_022436.3(ABCG5):c.1374C>G (p.Tyr458Ter) AND Sitosterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 30, 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:: RCV003611543.2

Allele description [Variation Report for NM_022436.3(ABCG5):c.1374C>G (p.Tyr458Ter)]

NM_022436.3(ABCG5):c.1374C>G (p.Tyr458Ter)

Genes:

ABCG5:ATP binding cassette subfamily G member 5 [Gene - OMIM - HGNC]
DYNC2LI1:dynein cytoplasmic 2 light intermediate chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_022436.3(ABCG5):c.1374C>G (p.Tyr458Ter)

HGVS:

NC_000002.12:g.43822886G>C
NG_008883.1:g.20934C>G
NG_053008.1:g.53848G>C
NM_001348912.2:c.*16-4500G>C
NM_001348913.2:c.*16-4500G>C
NM_022436.3:c.1374C>GMANE SELECT
NP_071881.1:p.Tyr458Ter
LRG_1181t1:c.1374C>G
LRG_1181:g.20934C>G
LRG_1181p1:p.Tyr458Ter
NC_000002.11:g.44050025G>C
NC_000002.11:g.44050025G>C
NM_022436.2:c.1374C>G

Protein change:

Y458*

Links:

dbSNP: rs1558738919

NCBI 1000 Genomes Browser:

rs1558738919

Molecular consequence:

NM_001348912.2:c.*16-4500G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001348913.2:c.*16-4500G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_022436.3:c.1374C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Sitosterolemia (STSL)
Synonyms:: Retention of dietary cholesterol and abnormal retention of non-cholesterol sterols in the body; Phytosterolemia; Plant sterol storage disease
Identifiers:: MONDO: MONDO:0008863; MedGen: C0342907; Orphanet: 2882; OMIM: PS210250

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004510422	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 30, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34093240, 11138003, 25665839, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004510422

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 30, 2023)

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

Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study.

Fermo E, Vercellati C, Marcello AP, Keskin EY, Perrotta S, Zaninoni A, Brancaleoni V, Zanella A, Giannotta JA, Barcellini W, Bianchi P.

Front Physiol. 2021;12:684569. doi: 10.3389/fphys.2021.684569.

PubMed [citation]

PMID:: 34093240
PMCID:: PMC8176228

Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.

Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB.

Nat Genet. 2001 Jan;27(1):79-83.

PubMed [citation]

PMID:: 11138003
PMCID:: PMC1350991

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004510422.1

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

Description

This premature translational stop signal has been observed in individual(s) with sitosterolemia (PMID: 34093240). 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 disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 808732). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr458*) in the ABCG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCG5 are known to be pathogenic (PMID: 11138003, 25665839).

#	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: Nov 30, 2024

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