VCV001809349.1 - ClinVar

GRCh37/hg19 11q14.1-22.3(chr11:81478509-104667040)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 11q14.1-22.3(chr11:81478509-104667040)x1

Variation ID: 1809349 Accession: VCV001809349.1

Type and length

copy number loss, -

Location

Cytogenetic: 11q14.1-22.3 11: 81478509-104667040 (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	Oct 19, 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.
FZD4		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	77	501
DLG2		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	78	116
YAP1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	74	100
TMEM135		No evidence available	No evidence available	GRCh38 GRCh37	30	51
AMOTL1		-	-	GRCh38 GRCh37	82	102
ANGPTL5		-	-	GRCh38 GRCh37	21	50
ANKRD42		-	-	GRCh38 GRCh37	31	49
ANKRD49		-	-	GRCh38 GRCh37	-	35
ARHGAP42		-	-	GRCh38 GRCh37	42	91
BIRC2		-	-	GRCh38 GRCh37	44	70

There are 85 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	Oct 19, 2021	RCV002475722.1

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 (Oct 19, 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: SCV002772950.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Comment: This large interstitial deletion, based on size and gene content, is expected to cause phenotypic and/or developmental abnormalities. This deletion involves numerous genes including FZD4 … (more) This large interstitial deletion, based on size and gene content, is expected to cause phenotypic and/or developmental abnormalities. This deletion involves numerous genes including FZD4 (OMIM 604579) and YAP1 (OMIM 606608) and DLG2 (OMIM 603583). Haploinsufficiency of FZD4 is associated with autosomal dominant familial exudative vitreoretinopathy-1 (OMIM 133780; Li et al., Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5368-5381. PMID: 30452590; Tian et al., Mol Vis. 2019 Feb 7;25:60-69. PMID: 30820142), an inherited disorder characterized by the incomplete development of the retinal vasculature. Heterozygous sequence variants, as well as one large deletion involving YAP1 have been associated with autosomal dominant ocular coloboma with or without hearing impairment, cleft lip/palate, and/or intellectual disability (OMIM 120433; Williamson KA et al., Am J Hum Genet. 2014 Feb 6;94(2):295-302. PMID: 24462371; Holt et al., Sci Rep. 2017 Aug 11;7(1):7975. PMID: 28801591). In addition, there is emerging information suggesting deletions of this gene maybe a risk factor for neurodevelopmental disorders (Reggiani et al.Genome Med. 2017 Jul 19;9(1):67. PMID: 28724449; Di Gregorio et al.,Clin Genet. 2017 Oct;92(4):415-422., PMID: 28295210). Sequence variations and intragenic deletions of DLG2 are also being evaluated with regard to schizophrenia (Kushima et al., Mol Psychiatry. 2017 Mar;22(3):430-440., PMID: 27240532; Ingason et al. Transl Psychiatry. 2015 Oct 13;5:e656. PMID: 26460480; Georgieva et al. Hum Mol Genet. 2014 Dec 15;23(24):6677-83. PMID: 25055870). A single publication identified a similar de novo deletion of 11q14.2q22.1 in a 13-year-old boy with severe learning difficulties, intellectual disability and mild heart defects (Papoulidis et al., Mol Cytogenet.2015 Sep 17;8:71. PMID: 26388939). The authors summarized previously published deletions over this region of variable size and gene content. They implicated GRM5 (encompassed in this deletion) and GRIA4 (not encompassed) in association with severity of developmental delay. The other features were variable and genotype-phenotype correlation could not be established. Further, this deletion interval includes genes that are associated with autosomal dominant phenotypes: TYR (OMIM 601800), TRPC6 (OMIM 603965) and autosomal recessive phenotypes: CTSC (OMIM 245010, 245000, 170650), MRE11 (OMIM 604391), and MTMR2 (OMIM 601382). (less)

Comment:

This large interstitial deletion, based on size and gene content, is expected to cause phenotypic and/or developmental abnormalities. This deletion involves numerous genes including FZD4 (OMIM 604579) and YAP1 (OMIM 606608) and DLG2 (OMIM 603583). Haploinsufficiency of FZD4 is associated with autosomal dominant familial exudative vitreoretinopathy-1 (OMIM 133780; Li et al., Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5368-5381. PMID: 30452590; Tian et al., Mol Vis. 2019 Feb 7;25:60-69. PMID: 30820142), an inherited disorder characterized by the incomplete development of the retinal vasculature. Heterozygous sequence variants, as well as one large deletion involving YAP1 have been associated with autosomal dominant ocular coloboma with or without hearing impairment, cleft lip/palate, and/or intellectual disability (OMIM 120433; Williamson KA et al., Am J Hum Genet. 2014 Feb 6;94(2):295-302. PMID: 24462371; Holt et al., Sci Rep. 2017 Aug 11;7(1):7975. PMID: 28801591). In addition, there is emerging information suggesting deletions of this gene maybe a risk factor for neurodevelopmental disorders (Reggiani et al.Genome Med. 2017 Jul 19;9(1):67. PMID: 28724449; Di Gregorio et al.,Clin Genet. 2017 Oct;92(4):415-422., PMID: 28295210). Sequence variations and intragenic deletions of DLG2 are also being evaluated with regard to schizophrenia (Kushima et al., Mol Psychiatry. 2017 Mar;22(3):430-440., PMID: 27240532; Ingason et al. Transl Psychiatry. 2015 Oct 13;5:e656. PMID: 26460480; Georgieva et al. Hum Mol Genet. 2014 Dec 15;23(24):6677-83. PMID: 25055870). A single publication identified a similar de novo deletion of 11q14.2q22.1 in a 13-year-old boy with severe learning difficulties, intellectual disability and mild heart defects (Papoulidis et al., Mol Cytogenet.2015 Sep 17;8:71. PMID: 26388939). The authors summarized previously published deletions over this region of variable size and gene content. They implicated GRM5 (encompassed in this deletion) and GRIA4 (not encompassed) in association with severity of developmental delay. The other features were variable and genotype-phenotype correlation could not be established. Further, this deletion interval includes genes that are associated with autosomal dominant phenotypes: TYR (OMIM 601800), TRPC6 (OMIM 603965) and autosomal recessive phenotypes: CTSC (OMIM 245010, 245000, 170650), MRE11 (OMIM 604391), and MTMR2 (OMIM 601382).

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 Mar 26, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 11q14.1-22.3(chr11:81478509-104667040)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...