VCV002671607.1 - 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: 2671607 Accession: VCV002671607.1

Type and length

Duplication, 34,668,642 bp

Location

Cytogenetic: 12p13.33-11.1 12: 188053-34856694 (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 17, 2023	Dec 17, 2023	Mar 16, 2023

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.
PTHLH		Sufficient evidence for dosage pathogenicity	Little evidence for dosage pathogenicity	GRCh38 GRCh37	84	114
CDKN1B		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	935	986
ETV6		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	295	402
GRIN2B		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1529	1572
PKP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1941	1994
SOX5		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	246	296
CACNA1C		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	2105	3075
CHD4		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	542	591
GUCY2C		No evidence available	No evidence available	GRCh38 GRCh37	337	759
KRAS		No evidence available	No evidence available	GRCh38 GRCh37	463	521

There are 270 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	Mar 16, 2023	RCV003448692.1

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 (Mar 16, 2023)	criteria provided, single submitter (ICSL CNVClassificationCriteria Aug2020) Method: clinical testing	Not Provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV004176334.1 First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023	Comment: This CNV is a 34.7 Mb duplication of 12p on chromosome 12, (seq[GRCh37]dup(12)(p13.33p11.1); chr12:g.188053_34856694dup), which is apparently mosaic. The CNV constitutes a gain encompassing 280 … (more) This CNV is a 34.7 Mb duplication of 12p on chromosome 12, (seq[GRCh37]dup(12)(p13.33p11.1); chr12:g.188053_34856694dup), which is apparently mosaic. The CNV constitutes a gain encompassing 280 protein coding genes, and overlaps the critical region associated with both mosaic 12p trisomy and Pallister-Killian syndrome. This critical region is located at 12p13.31 and contains the candidate genes ING4, CHD4, and MAGP2, though causality has not yet been ascribed to a specific gene (PMID: 34073526). Similar mosaic CNVs have been reported in individuals with developmental delays, hypotonia, digital anomalies, congenital heart defects, and variable craniofacial features (PMID: 16502429; PMID: 31913574). The 12p duplication has not been reported in published controls. Based on the available evidence, this CNV is classified as pathogenic. (less)

Comment:

This CNV is a 34.7 Mb duplication of 12p on chromosome 12, (seq[GRCh37]dup(12)(p13.33p11.1); chr12:g.188053_34856694dup), which is apparently mosaic. The CNV constitutes a gain encompassing 280 protein coding genes, and overlaps the critical region associated with both mosaic 12p trisomy and Pallister-Killian syndrome. This critical region is located at 12p13.31 and contains the candidate genes ING4, CHD4, and MAGP2, though causality has not yet been ascribed to a specific gene (PMID: 34073526). Similar mosaic CNVs have been reported in individuals with developmental delays, hypotonia, digital anomalies, congenital heart defects, and variable craniofacial features (PMID: 16502429; PMID: 31913574). The 12p duplication has not been reported in published controls. Based on the available evidence, this CNV is classified as pathogenic.

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 17, 2023

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 ...