VCV000580918.3 - ClinVar

NC_000005.9:g.112001178_112043328del

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

NC_000005.9:g.112001178_112043328del

Variation ID: 580918 Accession: VCV000580918.3

Type and length

Deletion, 42,151 bp

Location

Cytogenetic: 5q22.2 5: 112665481-112707631 (GRCh38) [ NCBI UCSC ] 5: 112001178-112043328 (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	May 16, 2022	May 16, 2022	May 30, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NC_000005.10:g.112665481_112707631del
NC_000005.9:g.112001178_112043328del

Protein change

Other names

Canonical SPDI

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.
APC		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	14969	15107
LOC102467216	-	-	-	GRCh38	-	15
LOC121079956	-	-	-	GRCh38	-	16
LOC123497954	-	-	-	GRCh38	-	15
LOC129994371	-	-	-	GRCh38	-	109

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.
Familial adenomatous polyposis 1	Likely pathogenic (1)	criteria provided, single submitter	May 30, 2018	RCV004564433.2

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.
Likely pathogenic (May 30, 2018)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Familial adenomatous polyposis 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000833549.2 First in ClinVar: Oct 10, 2018 Last updated: May 16, 2022	Publications: PubMed (5) PubMed: 28492532‚ 25243319‚ 21643010‚ 24946964‚ 23725351 Comment: This variant is a partial deletion of the genomic region encompassing the promoter 1B sequence of the APC gene. The 5' end of this event … (more) This variant is a partial deletion of the genomic region encompassing the promoter 1B sequence of the APC gene. The 5' end of this event is unknown as it extends beyond the assayed region for this gene, and therefore may encompass additional genes. The 3' boundary lies within the promoter 1B region of the APC gene. Gross deletions of the two APC promoter regions are known to be pathogenic. Similar deletions involving only the promoter 1B region, including a similar partial deletion of the promoter 1B region, have been reported in the literature in several families affected with familial adenomatous polyposis (PMID: 25243319, 21643010, 24946964, 23725351). Allele-specific expression analysis has shown that a similar partial deletion of the promoter 1B region reduced APC mRNA expression in patient-derived samples (PMID: 21643010). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)

Comment:

This variant is a partial deletion of the genomic region encompassing the promoter 1B sequence of the APC gene. The 5' end of this event is unknown as it extends beyond the assayed region for this gene, and therefore may encompass additional genes. The 3' boundary lies within the promoter 1B region of the APC gene. Gross deletions of the two APC promoter regions are known to be pathogenic. Similar deletions involving only the promoter 1B region, including a similar partial deletion of the promoter 1B region, have been reported in the literature in several families affected with familial adenomatous polyposis (PMID: 25243319, 21643010, 24946964, 23725351). Allele-specific expression analysis has shown that a similar partial deletion of the promoter 1B region reduced APC mRNA expression in patient-derived samples (PMID: 21643010). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been 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

Title	Author	Journal	Year	Link
APC promoter 1B deletion in seven American families with familial adenomatous polyposis.	Snow AK	Clinical genetics	2015	PMID: 25243319
Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis.	Pavicic W	Genes, chromosomes & cancer	2014	PMID: 24946964
APC promoter 1B deletion in familial polyposis--implications for mutation-negative families.	Kadiyska TK	Clinical genetics	2014	PMID: 23725351
Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis.	Rohlin A	Oncogene	2011	PMID: 21643010

Text-mined citations for this variant ...

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NC_000005.9:g.112001178_112043328del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...