VCV000583807.5 - ClinVar

NC_000017.10:g.(?_6328760)_(6616672_?)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_000017.10:g.(?_6328760)_(6616672_?)del

Variation ID: 583807 Accession: VCV000583807.5

Type and length

Deletion, 287,913 bp

Location

Cytogenetic: 17p13.2-13.1 17: 6328760-6616672 (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 10, 2018	Jun 9, 2024	Mar 19, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000017.10:g.(?_6328760)_(6616672_?)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.
AIPL1		-	-	GRCh38 GRCh37	562	587
C17orf100	-	-	-	GRCh38 GRCh37	-	24
KIAA0753		-	-	GRCh38 GRCh37	422	447
MED31		-	-	GRCh38 GRCh37	5	30
PIMREG		-	-	GRCh38 GRCh37	21	48
PITPNM3		-	-	GRCh38 GRCh37	878	914
SLC13A5		-	-	GRCh38 GRCh37	731	757
TXNDC17		-	-	GRCh38 GRCh37	7	32

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.
Developmental and epileptic encephalopathy, 25	Pathogenic (1)	criteria provided, single submitter	Dec 11, 2018	RCV000708070.3
Leber congenital amaurosis 4	Pathogenic (1)	criteria provided, single submitter	Mar 19, 2022	RCV001386952.4

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 11, 2018)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Epileptic encephalopathy, early infantile, 25 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000837180.2 First in ClinVar: Oct 10, 2018 Last updated: Aug 13, 2019	Publications: PubMed (1) PubMed: 28492532 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the SLC13A5 gene has been identified. The boundaries of this event are … (more) A gross deletion of the genomic region encompassing the full coding sequence of the SLC13A5 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with SLC13A5-related disease. Loss-of-function variants in SLC13A5 are known to be pathogenic (PMID: 24995870, 26384929). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 19, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Leber congenital amaurosis 4 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001587382.3 First in ClinVar: May 10, 2021 Last updated: Jun 09, 2024	Publications: PubMed (3) PubMed: 10615133‚ 15249368‚ 15347646 Comment: For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with AIPL1-related conditions. … (more) For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with AIPL1-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the AIPL1 gene has been identified. Loss-of-function variants in AIPL1 are known to be pathogenic (PMID: 10615133, 15249368, 15347646). 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 SLC13A5 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with SLC13A5-related disease. Loss-of-function variants in SLC13A5 are known to be pathogenic (PMID: 24995870, 26384929). For these reasons, this variant has been classified as Pathogenic.

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with AIPL1-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the AIPL1 gene has been identified. Loss-of-function variants in AIPL1 are known to be pathogenic (PMID: 10615133, 15249368, 15347646). 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
The Leber congenital amaurosis protein AIPL1 modulates the nuclear translocation of NUB1 and suppresses inclusion formation by NUB1 fragments.	van der Spuy J	The Journal of biological chemistry	2004	PMID: 15347646
The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations.	Dharmaraj S	Archives of ophthalmology (Chicago, Ill. : 1960)	2004	PMID: 15249368
Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.	Sohocki MM	Nature genetics	2000	PMID: 10615133

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000017.10:g.(?_6328760)_(6616672_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...