NM_001003694.2(BRPF1):c.1217dup (p.Tyr406Ter) AND Intellectual developmental disorder with dysmorphic facies and ptosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 28, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002472125.1

Allele description [Variation Report for NM_001003694.2(BRPF1):c.1217dup (p.Tyr406Ter)]

NM_001003694.2(BRPF1):c.1217dup (p.Tyr406Ter)

Gene:

BRPF1:bromodomain and PHD finger containing 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_001003694.2(BRPF1):c.1217dup (p.Tyr406Ter)

HGVS:

NC_000003.12:g.9739616dup
NG_052955.1:g.12888dup
NM_001003694.2:c.1217dupMANE SELECT
NM_001319049.2:c.1217dup
NM_001319050.2:c.1217dup
NM_001410704.1:c.1217dup
NM_004634.3:c.1217dup
NP_001003694.1:p.Tyr406Ter
NP_001305978.1:p.Tyr406Ter
NP_001305979.1:p.Tyr406Ter
NP_001397633.1:p.Tyr406Terfs
NP_004625.2:p.Tyr406Ter
NC_000003.11:g.9781300dup
NM_001003694.1:c.1217dupA
NR_160918.1:n.1631dup

Protein change:

Y406*

Molecular consequence:

NM_001410704.1:c.1217dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_160918.1:n.1631dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001003694.2:c.1217dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001319049.2:c.1217dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001319050.2:c.1217dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001410704.1:c.1217dup - nonsense - [Sequence Ontology: SO:0001587]
NM_004634.3:c.1217dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP)
Identifiers:: MONDO: MONDO:0015022; MedGen: C4310617; OMIM: 617333

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002768546	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 28, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002768546

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 28, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002768546.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

A heterozygous nonsense variant was identified, NM_001003694.1(BRPF1):c.1217dup in exon 3 of 14 of the BRPF1 gene. This nonsense variant is predicted to create a change of tyrosine to a stop at amino acid position 406 of the protein, NP_001003694.1(BRPF1):p.(Tyr406*), resulting in the loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a frequency of 0.0004% (1 heterozygote, 0 homozygotes). The variant has not been previously reported in clinical cases, however a different nucleotide change resulting in a stop at the same codon has been reported as Pathogenic in ClinVar. Other variants predicted to cause NMD have been reported as pathogenic in individuals with Intellectual developmental disorder with dysmorphic facies and ptosis (ClinVar). Based on information available at the time of curation, this variant has been classified as PATHOGENIC.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2022

ClinVar

Relating variation to medicine