VCV000979440.2 - ClinVar

GRCh37/hg19 16p11.2(chr16:28488319-30178406)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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 16p11.2(chr16:28488319-30178406)x1

Variation ID: 979440 Accession: VCV000979440.2

Type and length

copy number loss, 1,690,088 bp

Location

Cytogenetic: 16p11.2 16: 28488319-30178406 (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	Feb 13, 2022	Feb 13, 2022	Jan 4, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000016.9:g.(?_28488319)_(30178406_?)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.
PRRT2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	8	902
SH2B1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	359	515
ALDOA		-	-	GRCh38 GRCh37	1	561
APOBR		-	-	GRCh38 GRCh37	43	131
ASPHD1	-	-	-	GRCh38 GRCh37	20	313
ATP2A1		-	-	GRCh38 GRCh37	771	970
ATXN2L		-	-	GRCh38 GRCh37	46	204
BOLA2		-	-	GRCh38 GRCh37	-	87
C16orf54	-	-	-	GRCh38 GRCh37	1	276
C16orf92		-	-	GRCh38 GRCh37	2	297

There are 36 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)	no assertion criteria provided	Jan 4, 2021	RCV001258616.2

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 (Jan 04, 2021)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV001435585.2 First in ClinVar: Oct 07, 2020 Last updated: Feb 13, 2022	Comment: This copy number variant (CNV) includes 73 genes and is expected to cause phenotypic and/or developmental abnormalities. Recurrent deletions of 16p11.2 that include the SH2B1 … (more) This copy number variant (CNV) includes 73 genes and is expected to cause phenotypic and/or developmental abnormalities. Recurrent deletions of 16p11.2 that include the SH2B1 gene (OMIM 608937) are associated with developmental delay and obesity (Bachmann-Gagescu, et al., Genet Med. 2010 Oct;12(10):641-7, PMID: 20808231; Walters, et al., Nature. 2010 Feb 4;463(7281):671-5, PMID: 20130649) with variable penetrance. Although this deletion represents a recurrent highly penetrant copy number loss, similar deletions have also been detected in phenotypically normal parents of affected offspring (Ghasemi et al., Scand J Clin Lab Invest. 2012 Nov;72(7):523-30, PMID:23050497). This deletion interval also includes the region that is associated with the chromosome 16p11.2 microdeletion syndrome (OMIM #611913). Individuals with the 16p11.2 deletion reveal a detrimental effect on cognition, language ability, and motor coordination; increased rates of autism spectrum disorder (ASD) and the broader ASD phenotype (social difficulties, communication difficulties, stereotyped and repetitive behaviors and interests); patients with this deletion may present increased psychiatric difficulties compared with familial and population norms and may present facial dysmorphic features (Hanson, et al., Biol Psychiatry. 2015 May 1;77(9):785-93. PMID: 25064419). Similar 16p11.2 deletions have also been found in phenotypically normal parents due to incomplete penetrance and variable expressivity (Shinawi et al, 2010. J Med Genet 47: 332-341; PMID: 19914906& Walters et al, Nature. 2010 Feb 4;463(7281):671-5; PMID: 20130649). (less)

Comment:

This copy number variant (CNV) includes 73 genes and is expected to cause phenotypic and/or developmental abnormalities. Recurrent deletions of 16p11.2 that include the SH2B1 gene (OMIM 608937) are associated with developmental delay and obesity (Bachmann-Gagescu, et al., Genet Med. 2010 Oct;12(10):641-7, PMID: 20808231; Walters, et al., Nature. 2010 Feb 4;463(7281):671-5, PMID: 20130649) with variable penetrance. Although this deletion represents a recurrent highly penetrant copy number loss, similar deletions have also been detected in phenotypically normal parents of affected offspring (Ghasemi et al., Scand J Clin Lab Invest. 2012 Nov;72(7):523-30, PMID:23050497). This deletion interval also includes the region that is associated with the chromosome 16p11.2 microdeletion syndrome (OMIM #611913). Individuals with the 16p11.2 deletion reveal a detrimental effect on cognition, language ability, and motor coordination; increased rates of autism spectrum disorder (ASD) and the broader ASD phenotype (social difficulties, communication difficulties, stereotyped and repetitive behaviors and interests); patients with this deletion may present increased psychiatric difficulties compared with familial and population norms and may present facial dysmorphic features (Hanson, et al., Biol Psychiatry. 2015 May 1;77(9):785-93. PMID: 25064419). Similar 16p11.2 deletions have also been found in phenotypically normal parents due to incomplete penetrance and variable expressivity (Shinawi et al, 2010. J Med Genet 47: 332-341; PMID: 19914906& Walters et al, Nature. 2010 Feb 4;463(7281):671-5; PMID: 20130649).

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 Apr 25, 2022

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 16p11.2(chr16:28488319-30178406)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...