VCV001455963.4 - ClinVar

NC_000016.9:g.(?_3293141)_(3929917_?)del

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

NC_000016.9:g.(?_3293141)_(3929917_?)del

Variation ID: 1455963 Accession: VCV001455963.4

Type and length

Deletion, 636,777 bp

Location

Cytogenetic: 16p13.3 16: 3293141-3929917 (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	Mar 28, 2022	Jun 9, 2024	Oct 13, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000016.9:g.(?_3293141)_(3929917_?)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.
CREBBP		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2459	2577
DNASE1		No evidence available	No evidence available	GRCh38 GRCh37	49	238
MEFV		No evidence available	No evidence available	GRCh38 GRCh37	961	1263
C16orf90	-	-	-	GRCh38 GRCh37	-	47
CLUAP1		-	-	GRCh38 GRCh37	368	437
MTRNR2L4	-	-	-	GRCh38 GRCh37	3	48
NAA60		-	-	GRCh38 GRCh37	21	67
NLRC3		-	-	GRCh38 GRCh37	132	187
OR2C1	-	-	-	GRCh38 GRCh37	15	60
SLX4		-	-	GRCh38 GRCh37	2177	2239

There are 7 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.
Rubinstein-Taybi syndrome	Pathogenic (1)	criteria provided, single submitter	Oct 13, 2021	RCV001950905.6

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 13, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Rubinstein-Taybi syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002237268.4 First in ClinVar: Mar 28, 2022 Last updated: Jun 09, 2024	Publications: PubMed (6) PubMed: 27257017‚ 12114483‚ 17855048‚ 25805166‚ 17052327‚ 18792986 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the CREBBP gene has been identified. The boundaries of this event are … (more) A gross deletion of the genomic region encompassing the full coding sequence of the CREBBP gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletion of CREBBP has been reported to be de novo in the literature in an individual with growth retardation and other developmental abnormalities (PMID: 27257017). In addition, larger copy number events that include this gene have been reported in many individuals with Rubinstein-Taybi syndrome (PMID: 12114483, 17855048, 25805166,¬†10602114).¬†ClinVar contains an entry for a similar variant (Variation ID: 375635). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CREBBP are known to be pathogenic (PMID: 17052327, 18792986). (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the CREBBP gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletion of CREBBP has been reported to be de novo in the literature in an individual with growth retardation and other developmental abnormalities (PMID: 27257017). In addition, larger copy number events that include this gene have been reported in many individuals with Rubinstein-Taybi syndrome (PMID: 12114483, 17855048, 25805166,¬†10602114).¬†ClinVar contains an entry for a similar variant (Variation ID: 375635). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CREBBP are known to be pathogenic (PMID: 17052327, 18792986).

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

Title	Author	Journal	Year	Link
CNV analysis in Chinese children of mental retardation highlights a sex differentiation in parental contribution to de novo and inherited mutational burdens.	Wang B	Scientific reports	2016	PMID: 27257017
Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire.	Rusconi D	Human genetics	2015	PMID: 25805166
Genotype-phenotype correlations in Rubinstein-Taybi syndrome.	Schorry EK	American journal of medical genetics. Part A	2008	PMID: 18792986
High frequency of mosaic CREBBP deletions in Rubinstein-Taybi syndrome patients and mapping of somatic and germ-line breakpoints.	Gervasini C	Genomics	2007	PMID: 17855048
Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients.	Bentivegna A	BMC medical genetics	2006	PMID: 17052327
Molecular studies in 10 cases of Rubinstein-Taybi syndrome, including a mild variant showing a missense mutation in codon 1175 of CREBBP.	Bartsch O	Journal of medical genetics	2002	PMID: 12114483

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000016.9:g.(?_3293141)_(3929917_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...