VCV000617479.1 - 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.

Likely pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

Single allele

Variation ID: 617479 Accession: VCV000617479.1

Type and length

Complex, -

Location

Cytogenetic: 7q32.2-34 7: 129367205-140482957 (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	Jan 28, 2019	Jan 28, 2019	Jan 14, 2019

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.

variation affecting protein structure; Variation Ontology [ VariO:0060]

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.
BRAF		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1254	1368
UBN2		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	95	154
CPA4		No evidence available	No evidence available	GRCh38 GRCh37	32	58
KLF14		No evidence available	No evidence available	GRCh38 GRCh37	31	63
MEST		No evidence available	No evidence available	GRCh38 GRCh37	15	45
ADCK2	-	-	-	GRCh38 GRCh37	47	91
AGBL3		-	-	GRCh38 GRCh37	47	96
AKR1B1		-	-	GRCh38 GRCh37	14	53
AKR1B10		-	-	GRCh38 GRCh37	19	53
AKR1B15		-	-	GRCh38 GRCh37	27	61

There are 66 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.
Renal transitional cell carcinoma	Likely pathogenic (1)	no assertion criteria provided	Jan 14, 2019	RCV000754611.2

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.
Likely pathogenic (Jan 14, 2019)	no assertion criteria provided Method: clinical testing	Renal transitional cell carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Molecular Pathology Diagnostics Labratory, University of Iowa Hospitals & Clinics Accession: SCV000864217.1 First in ClinVar: Jan 28, 2019 Last updated: Jan 28, 2019	Comment: This particular fusion has not been functionally characterized, however, Ross, 2016 analyzed 20,573 cases of solid tumors and detected BRAF fusions that contained the entire … (more) This particular fusion has not been functionally characterized, however, Ross, 2016 analyzed 20,573 cases of solid tumors and detected BRAF fusions that contained the entire kinase domain in fifty-five cases. BRAF fusions were shown to be activating and oncogenic (Ross, 2016; Botton, 2013; Ciampi, 2005; Jones, 2008; Palanisamy, 2010). (less) Clinical Features: Renal transitional cell carcinoma (present) Age: 60-69 years Sex: male Ethnicity/Population group: Caucasian Geographic origin: United States Method: Total RNA (250ng) was reverse transcribed to cDNA. Libraries were prepared using the Comprehensive Thyroid and Lung (CTL) FusionPlex Assay for Illumina Platform (ArcherDX) following the manufacturerâ€™s protocol (see Zheng et al. 2014 for principle) and sequenced using MiSeq and NextSeq (Illumina, San Diego, CA). Data was analyzed using the CTL Target Region File and vendor supplied software (Archer Analysis version 5.0). A minimum of five reads with three or more unique sequencing start sites that cross the breakpoints were set as the cutoff to call for strong evidence of fusions. Testing laboratory: FoundationOne Date variant was reported to submitter: 2015-11-24 Testing laboratory interpretation: Likely pathogenic

Comment:

This particular fusion has not been functionally characterized, however, Ross, 2016 analyzed 20,573 cases of solid tumors and detected BRAF fusions that contained the entire kinase domain in fifty-five cases. BRAF fusions were shown to be activating and oncogenic (Ross, 2016; Botton, 2013; Ciampi, 2005; Jones, 2008; Palanisamy, 2010).

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
variation affecting protein structure (VariO:0060)			Molecular Pathology Diagnostics Labratory, University of Iowa Hospitals & Clinics Accession: SCV000864217.1

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Urothelial carcinoma with an NRF1-BRAF rearrangement and response to targeted therapy.	Isaacson AL	Cold Spring Harbor molecular case studies	2019	PMID: 31010895

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

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 ...