VCV002584572.1 - ClinVar

NM_022436.3(ABCG5):c.576del (p.Ile193fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022436.3(ABCG5):c.576del (p.Ile193fs)

Variation ID: 2584572 Accession: VCV002584572.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 2p21 2: 43828041 (GRCh38) [ NCBI UCSC ] 2: 44055180 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 21, 2023	Oct 21, 2023	Feb 3, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_022436.3:c.576del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071881.1:p.Ile193fs	frameshift
NM_001348912.2:c.*671del		3 prime UTR
NM_001348913.2:c.*671del		3 prime UTR
NC_000002.12:g.43828041del
NC_000002.11:g.44055180del
NG_008883.1:g.15779del
NG_008884.2:g.1100del
NG_053008.1:g.59003del
LRG_1181:g.15779del
LRG_1181t1:c.576del	LRG_1181p1:p.Ile193fs
LRG_1182:g.1100del

... more HGVS ... less HGVS

Protein change

I193fs

Other names

Canonical SPDI

NC_000002.12:43828040:G:

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ABCG5		-	-	GRCh38 GRCh37	181	744
DYNC2LI1		-	-	GRCh38 GRCh37	168	689

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Short-rib thoracic dysplasia 15 with polydactyly Sitosterolemia 2	Likely pathogenic (1)	criteria provided, single submitter	Feb 3, 2023	RCV003336012.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Feb 03, 2023)	criteria provided, single submitter (NYGC Assertion Criteria 2020) Method: clinical testing	Sitosterolemia 2 Short-rib thoracic dysplasia 15 with polydactyly Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	New York Genome Center Accession: SCV004046502.1 First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023	Comment: The c.576del variant in ABCG5 has not previously been reported in the literature or public variant repositories (ClinVar and LOVD) and is absent from population … (more) The c.576del variant in ABCG5 has not previously been reported in the literature or public variant repositories (ClinVar and LOVD) and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All of Us), suggesting it is not a common benign variant in the populations represented in those databases. The c.576del variant in ABCG5 is located in exon 5 of this 13-exon gene, predicted to incorporate a premature termination codon (p.(Ile193PhefsTer34)), and is expected to result in loss-of-function via nonsense mediated decay. Multiple loss-of-function variants that are downstream to the c.576del variant have been reported in individuals with Familial Hypercholesterolemia in the literature [PMID: 32088153] and in ClinVar [ClinVar IDs: #30485 and #222478] in the context of sitosterolemia. Based on available evidence this c.576del, p.(Ile193PhefsTer34) variant identified in ABCG5 is classified as Likely Pathogenic. (less) Number of individuals with the variant: 1 Clinical Features: Hypercholesterolemia (present) Secondary finding: no

Comment:

The c.576del variant in ABCG5 has not previously been reported in the literature or public variant repositories (ClinVar and LOVD) and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All of Us), suggesting it is not a common benign variant in the populations represented in those databases. The c.576del variant in ABCG5 is located in exon 5 of this 13-exon gene, predicted to incorporate a premature termination codon (p.(Ile193PhefsTer34)), and is expected to result in loss-of-function via nonsense mediated decay. Multiple loss-of-function variants that are downstream to the c.576del variant have been reported in individuals with Familial Hypercholesterolemia in the literature [PMID: 32088153] and in ClinVar [ClinVar IDs: #30485 and #222478] in the context of sitosterolemia. Based on available evidence this c.576del, p.(Ile193PhefsTer34) variant identified in ABCG5 is classified as Likely Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_022436.3(ABCG5):c.576del (p.Ile193fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...