NM_022436.3(ABCG5):c.1166G>A (p.Arg389His) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 22, 2024
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:: RCV002326665.11

Allele description [Variation Report for NM_022436.3(ABCG5):c.1166G>A (p.Arg389His)]

NM_022436.3(ABCG5):c.1166G>A (p.Arg389His)

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.1166G>A (p.Arg389His)

HGVS:

NC_000002.12:g.43824071C>T
NG_008883.1:g.19749G>A
NG_053008.1:g.55033C>T
NM_001348912.2:c.*16-3315C>T
NM_001348913.2:c.*16-3315C>T
NM_022436.3:c.1166G>AMANE SELECT
NP_071881.1:p.Arg389His
LRG_1181t1:c.1166G>A
LRG_1181:g.19749G>A
LRG_1181p1:p.Arg389His
NC_000002.11:g.44051210C>T
NM_022436.2:c.1166G>A
Q9H222:p.Arg389His

Protein change:

R389H; ARG389HIS

Links:

UniProtKB: Q9H222#VAR_012245; OMIM: 605459.0005; dbSNP: rs119480069

NCBI 1000 Genomes Browser:

rs119480069

Molecular consequence:

NM_001348912.2:c.*16-3315C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001348913.2:c.*16-3315C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_022436.3:c.1166G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002627467	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 22, 2024)	germline	clinical testing	PubMed (19) [See all records that cite these PMIDs] 11138003, 15054092, 15375183, 20521169, 20543520, 25665839, 28203044, 28771437, 29353225, 30985648, 31060161, 31901240, 32862661, 33217533, 33642439, 34505049, 34969652, 35705271, 36229885 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002627467

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 22, 2024)

germline

clinical testing

PubMed (19)
[See all records that cite these PMIDs]

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

Citations

PubMed

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

Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking.

Graf GA, Cohen JC, Hobbs HH.

J Biol Chem. 2004 Jun 4;279(23):24881-8. Epub 2004 Mar 30.

PubMed [citation]

PMID:: 15054092

See all PubMed Citations (19)

Details of each submission

From Ambry Genetics, SCV002627467.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (19)

Description

The c.1166G>A (p.R389H) alteration is located in exon 9 (coding exon 9) of the ABCG5 gene. This alteration results from a G to A substitution at nucleotide position 1166, causing the arginine (R) at amino acid position 389 to be replaced by a histidine (H). Based on data from gnomAD, the A allele has an overall frequency of 0.015% (42/282856) total alleles studied. The highest observed frequency was 0.206% (41/19950) of East Asian alleles. This variant has been reported in the homozygous and compound heterozygous state in several individuals and families affected with sitosterolemia, being reported as a common cause of disease in Asian populations (Niu, 2010; Yagasaki, 2017; Huang, 2019; Nomura, 2020; Yamada, 2021; Xia, 2022; Zhang, 2022). This amino acid position is highly conserved in available vertebrate species. An in vitro study suggested this alteration may impact protein function (Graf, 2004). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is 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 26, 2024

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