VCV001807753.1 - ClinVar

GRCh37/hg19 18p11.32-11.21(chr18:136227-11283184)x1

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

GRCh37/hg19 18p11.32-11.21(chr18:136227-11283184)x1

Variation ID: 1807753 Accession: VCV001807753.1

Type and length

copy number loss, -

Location

Cytogenetic: 18p11.32-11.21 18: 136227-11283184 (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 31, 2022	Dec 31, 2022	Aug 26, 2021

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.
TGIF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	147	287
ADCYAP1		-	-	GRCh38 GRCh37	11	163
AKAIN1		-	-	GRCh38 GRCh37	4	126
ANKRD12		-	-	GRCh38 GRCh37	113	218
APCDD1		-	-	GRCh38 GRCh37	106	209
ARHGAP28		-	-	GRCh38 GRCh37	36	163
CETN1		-	-	GRCh38 GRCh37	8	161
CLUL1		-	-	GRCh38 GRCh37	27	187
COLEC12		-	-	GRCh38 GRCh37	52	200
DLGAP1		-	-	GRCh38 GRCh37	57	227

There are 33 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.
not provided	Pathogenic (1)	criteria provided, single submitter	Aug 26, 2021	RCV002472559.1

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.
Pathogenic (Aug 26, 2021)	criteria provided, single submitter (ACMG/ClinGen CNV Guidelines, 2019) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002772427.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Comment: The copy number loss of 18p11.32q11.1 is expected to cause phenotypic and/or developmental abnormalities. Hemizygous terminal deletions of the short arm of chromosome 18 are … (more) The copy number loss of 18p11.32q11.1 is expected to cause phenotypic and/or developmental abnormalities. Hemizygous terminal deletions of the short arm of chromosome 18 are associated with chromosome 18p deletion syndrome (OMIM 146390, also known as monosomy 18p), which is characterized by a broad spectrum of phenotypic abnormalities, including developmental delay, intellectual disability, behavioral problems, short stature, and distinctive craniofacial features. Monosomy 18p is frequently associated with holoprosencephaly (HPE4, OMIM 142946) due to haploinsufficiency of TGIF1 (OMIM 602630), which is encompassed in the current interval. The HPE4 phenotype shows significantly reduced penetrance and variable expressivity and can vary from classic HPE to mild forms (microforms) resulting in just hypotelorism and/or a solitary median maxillary central incisor (Mello 2019, Qi 2019, Yin 2017, Poelmans 2015, Yi 2014, Chen 2013, Keaton 2010, Wester 2006, Kantaputra 2006). References: Chen et al., Gene. 2013 Sep 25;527(2):636-41. PMID: 23850725 Kantaputra et al., Am J Med Genet A. 2006 Dec 1;140(23):2598-602., PMID: 17001671. Keaton et al., Mol Syndromol. 2010;1(5):211-222. PMID: 22125506. Mello et al., J Intellect Disabil Res. 2019 Mar;63(3):225-232. PMID: 30536814. Poelmans et al., Am J Med Genet A. 2015 Oct;167A(10):2451-8. PMID: 26080100. Qi et al., Medicine (Baltimore). 2019 Apr;98(14):e15027. PMID: 30946338. Wester et al., Am J Med Genet A. 2006 Jun 1;140(11):1164-71. PMID: 16691587. Yi et al., Gene. 2014 Jan 10;533(2):565-9. PMID: 24091065. Yin et al. J Obstet Gynaecol. 2017 Aug;37(6):804-806. PMID: 28513240. (less)

Comment:

The copy number loss of 18p11.32q11.1 is expected to cause phenotypic and/or developmental abnormalities. Hemizygous terminal deletions of the short arm of chromosome 18 are associated with chromosome 18p deletion syndrome (OMIM 146390, also known as monosomy 18p), which is characterized by a broad spectrum of phenotypic abnormalities, including developmental delay, intellectual disability, behavioral problems, short stature, and distinctive craniofacial features. Monosomy 18p is frequently associated with holoprosencephaly (HPE4, OMIM 142946) due to haploinsufficiency of TGIF1 (OMIM 602630), which is encompassed in the current interval. The HPE4 phenotype shows significantly reduced penetrance and variable expressivity and can vary from classic HPE to mild forms (microforms) resulting in just hypotelorism and/or a solitary median maxillary central incisor (Mello 2019, Qi 2019, Yin 2017, Poelmans 2015, Yi 2014, Chen 2013, Keaton 2010, Wester 2006, Kantaputra 2006). References: Chen et al., Gene. 2013 Sep 25;527(2):636-41. PMID: 23850725 Kantaputra et al., Am J Med Genet A. 2006 Dec 1;140(23):2598-602., PMID: 17001671. Keaton et al., Mol Syndromol. 2010;1(5):211-222. PMID: 22125506. Mello et al., J Intellect Disabil Res. 2019 Mar;63(3):225-232. PMID: 30536814. Poelmans et al., Am J Med Genet A. 2015 Oct;167A(10):2451-8. PMID: 26080100. Qi et al., Medicine (Baltimore). 2019 Apr;98(14):e15027. PMID: 30946338. Wester et al., Am J Med Genet A. 2006 Jun 1;140(11):1164-71. PMID: 16691587. Yi et al., Gene. 2014 Jan 10;533(2):565-9. PMID: 24091065. Yin et al. J Obstet Gynaecol. 2017 Aug;37(6):804-806. PMID: 28513240.

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 Dec 31, 2022

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 18p11.32-11.21(chr18:136227-11283184)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...