VCV002672220.1 - ClinVar

NM_001003694.2(BRPF1):c.2545_2566dup (p.Ala856delinsGlyTer)

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

NM_001003694.2(BRPF1):c.2545_2566dup (p.Ala856delinsGlyTer)

Variation ID: 2672220 Accession: VCV002672220.1

Type and length

Duplication, 22 bp

Location

Cytogenetic: 3p25.3 3: 9743806-9743807 (GRCh38) [ NCBI UCSC ] 3: 9785490-9785491 (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 25, 2023	Dec 24, 2023	Jul 10, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001003694.2:c.2545_2566dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001003694.1:p.Ala856delinsGlyTer	nonsense
NM_001319049.2:c.2527_2548dup	NP_001305978.1:p.Ala850delinsGlyTer	nonsense
NM_001319050.2:c.2524_2545dup	NP_001305979.1:p.Ala849delinsGlyTer	nonsense
NM_001410704.1:c.2542_2563dup	NP_001397633.1:p.Ala855delinsGlyTer	nonsense
NM_004634.3:c.2527_2548dup	NP_004625.2:p.Ala850delinsGlyTer	nonsense
NR_160918.1:n.3128_3149dup		non-coding transcript variant
NC_000003.12:g.9743811_9743832dup
NC_000003.11:g.9785495_9785516dup
NG_052955.1:g.17083_17104dup

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000003.12:9743806:CCGGGGTAGTCTGACACCCCACCCGG:CCGGGGTAGTCTGACACCCCACCCGGGGTAGTCTGACACCCCACCCGG

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.
BRPF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	353	413

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.
Intellectual developmental disorder with dysmorphic facies and ptosis	Pathogenic (1)	criteria provided, single submitter	Jul 10, 2023	RCV003459022.1

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 (Jul 10, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Intellectual developmental disorder with dysmorphic facies and ptosis Affected status: yes Allele origin: germline	Clinical Genomics Laboratory, Washington University in St. Louis Accession: SCV004177197.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Comment: The BRPF1 c.2545_2566dup (p.Ala856fs) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), … (more) The BRPF1 c.2545_2566dup (p.Ala856fs) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by duplicating 22 nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Additionally, other frameshifts in this region have been described in affected individuals and are considered pathogenic (Zu G et al., PMID: 36077605). Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as pathogenic. (less)

Comment:

The BRPF1 c.2545_2566dup (p.Ala856fs) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by duplicating 22 nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Additionally, other frameshifts in this region have been described in affected individuals and are considered pathogenic (Zu G et al., PMID: 36077605). Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant 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 30, 2023

ClinVar Genomic variation as it relates to human health

NM_001003694.2(BRPF1):c.2545_2566dup (p.Ala856delinsGlyTer)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...