VCV001703234.1 - ClinVar

Single allele

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

Single allele

Variation ID: 1703234 Accession: VCV001703234.1

Type and length

Deletion, 18,757,308 bp

Location

Cytogenetic: 18q21.33-23 18: 61490305-80247612 (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	Sep 3, 2022	Sep 3, 2022	Aug 25, 2022

HGVS

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.
GALR1		No evidence available	No evidence available	GRCh38 GRCh37	27	197
ZNF407		No evidence available	No evidence available	GRCh38 GRCh37	309	530
ADNP2		-	-	GRCh38 GRCh37	83	259
ATP9B		-	-	GRCh38 GRCh37	99	280
BCL2		-	-	GRCh38 GRCh37	6	99
C18orf63	-	-	-	GRCh38 GRCh37	3	158
CBLN2		-	-	GRCh38 GRCh37	16	162
CCDC102B	-	-	-	GRCh38 GRCh37	48	200
CD226		-	-	GRCh38 GRCh37	17	158
CDH19		-	-	GRCh38 GRCh37	89	207

There are 422 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.
Deletion of long arm of chromosome 18	Pathogenic (1)	criteria provided, single submitter	Aug 25, 2022	RCV002280357.3

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 (Aug 25, 2022)	criteria provided, single submitter (ACMG/ClinGen CNV Guidelines, 2019) Method: curation	Deletion of long arm of chromosome 18 (Sporadic) Affected status: yes Allele origin: germline	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Accession: SCV002568413.1 First in ClinVar: Sep 03, 2022 Last updated: Sep 03, 2022	Comment: A confirmed de novo heterozygous deletion of 18q21.33-q23 ([GRCh38]61,490,305_80,247,612x1) encompassing 129 genes was identified by whole exome sequencing of one individual with global developmental delay, … (more) A confirmed de novo heterozygous deletion of 18q21.33-q23 ([GRCh38]61,490,305_80,247,612x1) encompassing 129 genes was identified by whole exome sequencing of one individual with global developmental delay, delayed speech and language development, dystonia, delayed gross and fine motor development, steppage gait, and abnormal social behavior via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). Data from large population studies is insufficient to assess the frequency of this variant. At least three probands from the literature (Yu et al. 2022, PMID: 21977138, PMID: 34616427) have a copy-number loss in 18q22.2q23 similar in genomic content to the variant in our study. Of these probands, two have deletions that are confirmed de novo, and the reported phenotypes are nonspecific (mild intellectual disability, developmental delay, motor delay, lack of expressive and receptive language). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Chromosome 18 Deletion Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2B: 0 points, 3C: 0.90 points, 4C: 0.40 points, 5A: 0.15 points; Total: 1.45 points; Riggs 2020 (PMID: 31690835). (less)

Comment:

A confirmed de novo heterozygous deletion of 18q21.33-q23 ([GRCh38]61,490,305_80,247,612x1) encompassing 129 genes was identified by whole exome sequencing of one individual with global developmental delay, delayed speech and language development, dystonia, delayed gross and fine motor development, steppage gait, and abnormal social behavior via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). Data from large population studies is insufficient to assess the frequency of this variant. At least three probands from the literature (Yu et al. 2022, PMID: 21977138, PMID: 34616427) have a copy-number loss in 18q22.2q23 similar in genomic content to the variant in our study. Of these probands, two have deletions that are confirmed de novo, and the reported phenotypes are nonspecific (mild intellectual disability, developmental delay, motor delay, lack of expressive and receptive language). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Chromosome 18 Deletion Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2B: 0 points, 3C: 0.90 points, 4C: 0.40 points, 5A: 0.15 points; Total: 1.45 points; Riggs 2020 (PMID: 31690835).

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 Sep 01, 2024

ClinVar Genomic variation as it relates to human health

Single allele

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...