VCV003250355.1 - ClinVar

NC_000015.10:g.(?_22786657)_(28299516_?)dup

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_000015.10:g.(?_22786657)_(28299516_?)dup

Variation ID: 3250355 Accession: VCV003250355.1

Type and length

Duplication, 5,512,860 bp

Location

Cytogenetic: 15q11.2-13.1 15: 22786657-28299516 (GRCh38) [ 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	Jul 7, 2024	Jul 7, 2024	Jun 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NC_000015.10:g.(?_22786657)_(28299516_?)dup

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.
UBE3A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	40	1234
MAGEL2		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	1055	1359
SNURF	-	Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	-	370
ATP10A		No evidence available	No evidence available	GRCh38 GRCh37	197	504
GABRB3		No evidence available	No evidence available	GRCh38 GRCh37	649	963
MKRN3		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	72	376
NDN		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	41	344
NIPA1		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	275	686
NIPA2		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	56	391
SNORD107	-	No evidence available	No evidence available	GRCh38	-	153

There are 154 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

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.
15q11q13 microduplication syndrome	Likely pathogenic (1)	criteria provided, single submitter	Jun 22, 2024	RCV004584574.1

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 (Jun 22, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	15q11q13 microduplication syndrome Affected status: yes Allele origin: germline	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics Accession: SCV005068265.1 First in ClinVar: Jul 07, 2024 Last updated: Jul 07, 2024	Comment: A contiguous homozygous duplication of size ~5512.86 kb on chromosome 15, [chr15:g.(?_22786657)_(28299516_?)dup] encompassing multiple genes suggestive of a copy number variant was detected. The read … (more) A contiguous homozygous duplication of size ~5512.86 kb on chromosome 15, [chr15:g.(?_22786657)_(28299516_?)dup] encompassing multiple genes suggestive of a copy number variant was detected. The read depth of these targeted regions is found to be higher than usual [CNV ratio: 1.83; BF value: 1490.00]. The results are likely to be suggestive of a homozygous duplication (copy number gain). Contiguous duplication overlapping these genes have previously been reported in the literature [PMID: 26022164]. In summary, the variant meets our criteria to be classified as likely pathogenic. (less) Clinical Features: Profound global developmental delay (present) , Hyperactivity (present) , Anemia (present) , Anisopoikilocytosis (present) , Hepatomegaly (present) , Widely spaced teeth (present) , Partial congenital … (more) Profound global developmental delay (present) , Hyperactivity (present) , Anemia (present) , Anisopoikilocytosis (present) , Hepatomegaly (present) , Widely spaced teeth (present) , Partial congenital absence of teeth (present) (less) Age: 0-9 years Sex: female Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on the Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication

Comment:

A contiguous homozygous duplication of size ~5512.86 kb on chromosome 15, [chr15:g.(?_22786657)_(28299516_?)dup] encompassing multiple genes suggestive of a copy number variant was detected. The read depth of these targeted regions is found to be higher than usual [CNV ratio: 1.83; BF value: 1490.00]. The results are likely to be suggestive of a homozygous duplication (copy number gain). Contiguous duplication overlapping these genes have previously been reported in the literature [PMID: 26022164]. In summary, the variant meets our criteria to be 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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Jul 15, 2024

ClinVar Genomic variation as it relates to human health

NC_000015.10:g.(?_22786657)_(28299516_?)dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...