VCV002678310.2 - ClinVar

NM_003742.4(ABCB11):c.2542del (p.Asp848fs)

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.

(2)

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.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003742.4(ABCB11):c.2542del (p.Asp848fs)

Variation ID: 2678310 Accession: VCV002678310.2

Type and length

Deletion, 1 bp

Location

Cytogenetic: 2q31.1 2: 168944673 (GRCh38) [ NCBI UCSC ] 2: 169801183 (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	Dec 30, 2023	Feb 28, 2024	Nov 10, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_003742.4:c.2542del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003733.2:p.Asp848fs	frameshift
NC_000002.12:g.168944673del
NC_000002.11:g.169801183del
NG_007374.2:g.91724del
LRG_1199:g.91724del
LRG_1199t1:c.2542del	LRG_1199p1:p.Asp848fs

... more HGVS ... less HGVS

Protein change

D848fs

Other names

Canonical SPDI

NC_000002.12:168944672:C:

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.
ABCB11		-	-	GRCh38 GRCh38 GRCh37	1502	1605

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.
Benign recurrent intrahepatic cholestasis type 2	Pathogenic (1)	criteria provided, single submitter	Oct 13, 2023	RCV003463500.1
not provided	Pathogenic (1)	criteria provided, single submitter	Nov 10, 2023	RCV003779097.2

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.
Pathogenic (Oct 13, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Benign recurrent intrahepatic cholestasis type 2 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004208625.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Pathogenic (Nov 10, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004655137.1 First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024	Publications: PubMed (3) PubMed: 18395098‚ 20232290‚ 34016879 Comment: This sequence change creates a premature translational stop signal (p.Asp848Metfs10) in the ABCB11 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Asp848Metfs10) in the ABCB11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB11 are known to be pathogenic (PMID: 18395098, 20232290). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ABCB11-related conditions (PMID: 34016879). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Asp848Metfs*10) in the ABCB11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB11 are known to be pathogenic (PMID: 18395098, 20232290). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ABCB11-related conditions (PMID: 34016879). For these reasons, this variant has been classified as 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

Title	Author	Journal	Year	Link
Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children With Monogenic Cholestasis.	Hertel PM	Journal of pediatric gastroenterology and nutrition	2021	PMID: 34016879
ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history.	Davit-Spraul A	Hepatology (Baltimore, Md.)	2010	PMID: 20232290
Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.	Strautnieks SS	Gastroenterology	2008	PMID: 18395098

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_003742.4(ABCB11):c.2542del (p.Asp848fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...