VCV000180280.59 - ClinVar

NM_000384.3(APOB):c.6636TGA[1] (p.Asp2213del)

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.

(19)

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.

Conflicting classifications of pathogenicity
Uncertain significance(3); Benign(7); Likely benign(7)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000384.3(APOB):c.6636TGA[1] (p.Asp2213del)

Variation ID: 180280 Accession: VCV000180280.59

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: 2p24.1 2: 21010227-21010229 (GRCh38) [ NCBI UCSC ] 2: 21233099-21233101 (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	Feb 7, 2015	Oct 20, 2024	Jul 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000384.3:c.6636TGA[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000375.3:p.Asp2213del	inframe deletion
NM_000384.2:c.6639_6641delTGA
NC_000002.12:g.21010227TCA[1]
NC_000002.11:g.21233099TCA[1]
NG_011793.1:g.38842TGA[1]

... more HGVS ... less HGVS

Protein change

D2213del

Other names

Canonical SPDI

NC_000002.12:21010226:TCATCA:TCA

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.

0.00180 (TCA)

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

Links

ClinGen: CA022887 dbSNP: rs541497967 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.
APOB		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	3553	3756

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.
Hypercholesterolemia, familial, 1	Conflicting interpretations of pathogenicity (7)	criteria provided, conflicting classifications	Jan 2, 2018	RCV000157119.23
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jul 1, 2024	RCV000471850.42
not specified	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jul 6, 2017	RCV000181039.21
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	May 9, 2017	RCV002362835.9
Familial hypercholesterolemia	Benign (2)	criteria provided, multiple submitters, no conflicts	Dec 19, 2023	RCV000776056.11
APOB-related disorder	Likely benign (1)	no assertion criteria provided	Nov 14, 2019	RCV004535019.2
Hypercholesterolemia, autosomal dominant, type B	Likely benign (1)	criteria provided, single submitter	Jan 1, 2019	RCV001262209.9
Familial hypobetalipoproteinemia 1 Hypercholesterolemia, autosomal dominant, type B	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV001837464.13

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.
Uncertain significance (Mar 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Familial hypercholesterolemia Affected status: yes Allele origin: germline	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge Accession: SCV000322847.1 First in ClinVar: Feb 07, 2015 Last updated: Feb 07, 2015	Comment: 1/96 normolipidaemic Portuguese controls Observation 1: Comment on evidence: %MAF (ExAC):0.5167 Observation 2:
Benign (Mar 28, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538311.1 First in ClinVar: Jul 24, 2016 Last updated: Jul 24, 2016	Comment: Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more) Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 1.9% (122/6498) Finnish chromosomes (less) Method: Genome/Exome Filtration
Likely benign (Jan 02, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercholesterolemia, familial, 1 (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Robarts Research Institute, Western University Accession: SCV000782873.1 First in ClinVar: May 19, 2018 Last updated: May 19, 2018
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Familial hypobetalipoproteinemia 1 Hypercholesterolemia, autosomal dominant, type B 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	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000554839.9 First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024
Likely benign (-)	criteria provided, single submitter (Submitter's publication) Method: research	Familial Hypercholesterolemia (Autosomal dominant inheritance) Affected status: no Allele origin: germline	Institute for Integrative and Experimental Genomics, University of Luebeck Accession: SCV000212147.1 First in ClinVar: Feb 07, 2015 Last updated: Feb 07, 2015	Publications: PubMed (1) PubMed: 26036859
Uncertain significance (Mar 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Familial hypercholesterolemia Affected status: unknown Allele origin: germline	Laboratory of Genetics and Molecular Cardiology, University of São Paulo Study: HipercolBrasil Accession: SCV000588440.1 First in ClinVar: Aug 13, 2017 Last updated: Aug 13, 2017	Comment on evidence: %MAF(ExAC):0.5167
Likely benign (Jul 06, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: yes Allele origin: germline	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute Accession: SCV000740414.1 First in ClinVar: Apr 14, 2018 Last updated: Apr 14, 2018
Uncertain significance (Mar 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Familial hypercholesterolemia Affected status: unknown Allele origin: germline	Iberoamerican FH Network Accession: SCV000748125.1 First in ClinVar: May 19, 2018 Last updated: May 19, 2018 Comment: Variant present in the database from Uruguay	Comment on evidence: %MAF(ExAC):0.5167
Benign (Mar 07, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial hypercholesterolemias Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000910691.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Likely benign (Jan 01, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercholesterolemia, autosomal dominant, type B Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001439996.1 First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020
Benign (Dec 31, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000233314.14 First in ClinVar: Jul 05, 2015 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 27153395, 9050776, 24234650, 23680767, 33111339)
Benign (Dec 07, 2018)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV001133414.5 First in ClinVar: Jan 04, 2020 Last updated: Jan 06, 2024	Publications: PubMed (3) PubMed: 24234650‚ 27153395‚ 23680767
Likely benign (Sep 29, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV004564135.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024
Benign (May 09, 2017)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002662183.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Dec 19, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial hypercholesterolemia Affected status: unknown Allele origin: germline	GENinCode PLC Accession: SCV005074052.1 First in ClinVar: Jul 15, 2024 Last updated: Jul 15, 2024
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Familial Hypercholesterolemia Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427053.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jul 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001152145.27 First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024	Comment: APOB: PM4:Supporting, BS2 Number of individuals with the variant: 12
Likely benign (Nov 14, 2019)	no assertion criteria provided Method: clinical testing	APOB-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004728672.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Uncertain significance (Oct 07, 2014)	no assertion criteria provided Method: clinical testing	Familial hypercholesterolemia Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV000206842.1 First in ClinVar: Feb 07, 2015 Last updated: Feb 07, 2015 Comment: Found together with likely pathogenic LDLR:NM_000527.4:c.1186+1G>T	Number of individuals with the variant: 1
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Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 1.9% (122/6498) Finnish chromosomes

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.	Maxwell KN	American journal of human genetics	2016	PMID: 27153395
Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction.	Brænne I	European journal of human genetics : EJHG	2016	PMID: 26036859
Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia.	Alves AC	Human molecular genetics	2014	PMID: 24234650
The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia.	Vandrovcova J	Genetics in medicine : official journal of the American College of Medical Genetics	2013	PMID: 23680767

Text-mined citations for rs541497967 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000384.3(APOB):c.6636TGA[1] (p.Asp2213del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs541497967 ...