NM_022436.3(ABCG5):c.1567A>G (p.Ile523Val) AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: May 7, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000595235.16

Allele description [Variation Report for NM_022436.3(ABCG5):c.1567A>G (p.Ile523Val)]

NM_022436.3(ABCG5):c.1567A>G (p.Ile523Val)

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.1567A>G (p.Ile523Val)

HGVS:

NC_000002.12:g.43819997T>C
NG_008883.1:g.23823A>G
NG_053008.1:g.50959T>C
NM_001348912.2:c.*16-7389T>C
NM_001348913.2:c.*16-7389T>C
NM_022436.3:c.1567A>GMANE SELECT
NP_071881.1:p.Ile523Val
LRG_1181t1:c.1567A>G
LRG_1181:g.23823A>G
LRG_1181p1:p.Ile523Val
NC_000002.11:g.44047136T>C
NM_022436.2:c.1567A>G

Protein change:

I523V

Links:

dbSNP: rs140899003

NCBI 1000 Genomes Browser:

rs140899003

Molecular consequence:

NM_001348912.2:c.*16-7389T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001348913.2:c.*16-7389T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_022436.3:c.1567A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000709628	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Jun 29, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001978780	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV002070903	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005185385	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 7, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24503134, 32088153 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias.

Johansen CT, Dubé JB, Loyzer MN, MacDonald A, Carter DE, McIntyre AD, Cao H, Wang J, Robinson JF, Hegele RA.

J Lipid Res. 2014 Apr;55(4):765-72. doi: 10.1194/jlr.D045963. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503134
PMCID:: PMC3966710

See all PubMed Citations (3)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000709628.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

#	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		2	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001978780.1

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

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

From Genetic Services Laboratory, University of Chicago, SCV002070903.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	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, SCV005185385.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: ABCG5 c.1567A>G (p.Ile523Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 1614184 control chromosomes in the gnomAD database, including 10 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCG5 causing Early Onset Coronary Artery Disease (0.0019 vs 0.005), allowing no conclusion about variant significance. c.1567A>G has been reported in the literaturein at-least one patient suspected of partial lipodystrophy without strong evidence for causality (example: Johansen_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Early Onset Coronary Artery Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 24503134, 32088153). ClinVar contains an entry for this variant (Variation ID: 502765). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

#	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 3, 2024

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