VCV000564326.3 - ClinVar

GRCh37/hg19 16p11.2(chr16:29591078-30243606)x3

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(chr16:29591078-30243606)x3

Variation ID: 564326 Accession: VCV000564326.3

Type and length

copy number gain, -

Location

Cytogenetic: 16p11.2 16: 29591078-30243606 (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	Mar 1, 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.
PRRT2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	8	904
ALDOA		-	-	GRCh38 GRCh37	1	561
ASPHD1	-	-	-	GRCh38 GRCh37	20	313
BOLA2B	-	-	-	GRCh38 GRCh37	-	98
C16orf54	-	-	-	GRCh38 GRCh37	1	276
C16orf92		-	-	GRCh38 GRCh37	2	297
CDIPT		-	-	GRCh38 GRCh37	13	299
CORO1A		-	-	GRCh38 GRCh37	241	473
DOC2A		-	-	GRCh38 GRCh37	31	315
GDPD3		-	-	GRCh38 GRCh37	22	311

There are 20 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	Mar 1, 2021	RCV000683815.3

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 (Mar 01, 2021)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000811324.3 First in ClinVar: Sep 30, 2018 Last updated: Feb 13, 2022	Comment: The copy number gain of 16p11.2 is consistent with the 16p11.2 microduplication syndrome (OMIM #614671). It exhibits incomplete penetrance and variable expressivity and is associated … (more) The copy number gain of 16p11.2 is consistent with the 16p11.2 microduplication syndrome (OMIM #614671). It exhibits incomplete penetrance and variable expressivity and is associated with susceptibility to autism as well as the potential for intellectual disability/developmental delay, ADHD, speech and language disorders, seizures, hypotonia, and coordination issues (Bernier et al. Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):367-380. PMID: 28349640; Steinman KJ, et al., Am J Med Genet A. 2016 Nov;170(11):2943-2955. PMID: 27410714; Weiss et al, N Engl J Med. 2008 Feb 14;358(7):667-75, PMID: 18184952; Fernandez et al., J Med Genet. 2010 Mar;47(3):195-203, PMID: 19755429; Shinawi et al, J Med Genet. 2010 47: 332-341, PMID: 19914906). Additionally, there are multiple reports of increased risks for neuropsychiatric disorders with 16p11. 2 duplications (Degenhardt et al., Am J Med Genet B Neuropsychiatr Genet. 2012;159B(3):263-73, PMID: 22344817; Steinberg S, et. al., Mol Psychiatry. 2014 Jan;19(1):108-14, PMID: 23164818). Further, a group recently evaluated neuroradiologic findings in a cohort of patients with duplications of 16p11.2 and noted thinner corpora callosa, decreased white matter volume and increased ventricular volume which were associated with decreased full-scale and verbal IQ scores compared with duplication carriers without these findings (Owen et al. Radiology. 2018 Jan;286(1):217-226. PMID: 28786752). Additionally, this copy number gain involves several genes associated with autosomal dominant OMIM phenotypes: (KIF22, PRRT2, TBX6) and two genes with autosomal recessive phenotypes (ALDOA, TBX6). (less)

Comment:

The copy number gain of 16p11.2 is consistent with the 16p11.2 microduplication syndrome (OMIM #614671). It exhibits incomplete penetrance and variable expressivity and is associated with susceptibility to autism as well as the potential for intellectual disability/developmental delay, ADHD, speech and language disorders, seizures, hypotonia, and coordination issues (Bernier et al. Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):367-380. PMID: 28349640; Steinman KJ, et al., Am J Med Genet A. 2016 Nov;170(11):2943-2955. PMID: 27410714; Weiss et al, N Engl J Med. 2008 Feb 14;358(7):667-75, PMID: 18184952; Fernandez et al., J Med Genet. 2010 Mar;47(3):195-203, PMID: 19755429; Shinawi et al, J Med Genet. 2010 47: 332-341, PMID: 19914906). Additionally, there are multiple reports of increased risks for neuropsychiatric disorders with 16p11. 2 duplications (Degenhardt et al., Am J Med Genet B Neuropsychiatr Genet. 2012;159B(3):263-73, PMID: 22344817; Steinberg S, et. al., Mol Psychiatry. 2014 Jan;19(1):108-14, PMID: 23164818). Further, a group recently evaluated neuroradiologic findings in a cohort of patients with duplications of 16p11.2 and noted thinner corpora callosa, decreased white matter volume and increased ventricular volume which were associated with decreased full-scale and verbal IQ scores compared with duplication carriers without these findings (Owen et al. Radiology. 2018 Jan;286(1):217-226. PMID: 28786752). Additionally, this copy number gain involves several genes associated with autosomal dominant OMIM phenotypes: (KIF22, PRRT2, TBX6) and two genes with autosomal recessive phenotypes (ALDOA, TBX6).

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(chr16:29591078-30243606)x3

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...