VCV000457359.45 - ClinVar

NC_000005.9:g.(?_86400000)_(154000000_?)del

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000005.9:g.(?_86400000)_(154000000_?)del

Variation ID: 457359 Accession: VCV000457359.45

Type and length

Deletion, 67,600,001 bp

Location

Cytogenetic: 5q14.3-33.2 5: 86400000-154000000 (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 26, 2017	Jun 9, 2024	Dec 3, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000005.9:g.(?_86400000)_(154000000_?)del

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.
MEF2C		Sufficient evidence for dosage pathogenicity	Little evidence for dosage pathogenicity	GRCh38 GRCh37	462	573
APC		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	14969	15107
CTNNA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2875	2934
LMNB1		No evidence available	Sufficient evidence for dosage pathogenicity	GRCh38 GRCh37	246	285
NR2F1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	170	397
POU4F3		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2	211
PURA		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	482	540
RASA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	293	1327
SPINK1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	203	224
TCOF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	841	880

There are 377 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

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.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Dec 3, 2021	RCV000554476.11
Familial adenomatous polyposis 1	Pathogenic (1)	criteria provided, single submitter	Dec 3, 2021	RCV004561496.2

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 (Dec 03, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000628128.2 First in ClinVar: Dec 26, 2017 Last updated: May 16, 2022	Publications: PubMed (1) PubMed: 19409520 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the RAD50 gene has been identified. Loss-of-function variants in RAD50 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the RAD50 gene has been identified. Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with RAD50-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Dec 03, 2021)	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: SCV001579408.5 First in ClinVar: May 10, 2021 Last updated: Jun 09, 2024	Publications: PubMed (5) PubMed: 18487285‚ 19279422‚ 21643010‚ 17963004‚ 20685668 Comment: For these reasons, this variant has been classified as Pathogenic. A similar copy number variant has been observed in individual(s) with familial adenomatous polyposis (PMID: … (more) For these reasons, this variant has been classified as Pathogenic. A similar copy number variant has been observed in individual(s) with familial adenomatous polyposis (PMID: 18487285, 19279422, 21643010). A gross deletion of the genomic region encompassing the full coding sequence of the APC gene has been identified. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the RAD50 gene has been identified. Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with RAD50-related conditions. For these reasons, this variant has been classified as Pathogenic.

Comment:

For these reasons, this variant has been classified as Pathogenic. A similar copy number variant has been observed in individual(s) with familial adenomatous polyposis (PMID: 18487285, 19279422, 21643010). A gross deletion of the genomic region encompassing the full coding sequence of the APC gene has been identified. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes.

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
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
Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP.	Lagarde A	Journal of medical genetics	2010	PMID: 20685668
Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder.	Waltes R	American journal of human genetics	2009	PMID: 19409520
Implication of adenomatous polyposis coli and MUTYH mutations in familial colorectal polyposis.	De Rosa M	Diseases of the colon and rectum	2009	PMID: 19279422
Detection of APC gene deletions using quantitative multiplex PCR of short fluorescent fragments.	Castellsagué E	Clinical chemistry	2008	PMID: 18487285
Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations.	De la Fuente MK	Diseases of the colon and rectum	2007	PMID: 17963004

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.(?_86400000)_(154000000_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...