NM_001042492.3(NF1):c.6921+1G>A AND Neurofibromatosis, type 1

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Aug 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000476980.9

Allele description [Variation Report for NM_001042492.3(NF1):c.6921+1G>A]

NM_001042492.3(NF1):c.6921+1G>A

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.6921+1G>A

HGVS:

NC_000017.11:g.31338806G>A
NG_009018.1:g.248830G>A
NM_000267.3:c.6858+1G>A
NM_001042492.3:c.6921+1G>AMANE SELECT
LRG_214t1:c.6858+1G>A
LRG_214t2:c.6921+1G>A
LRG_214:g.248830G>A
NC_000017.10:g.29665824G>A
NM_001042492.2:c.6921+1G>A
NM_001042492.3:c.6921+1G>A

Links:

dbSNP: rs1060500355

NCBI 1000 Genomes Browser:

rs1060500355

Molecular consequence:

NM_000267.3:c.6858+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001042492.3:c.6921+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Neurofibromatosis, type 1 (NF1)
Synonyms:: NEUROFIBROMATOSIS, TYPE I; Recklinghausen's disease; Von Recklinghausen disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000542170	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 6, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10607834, 11735023, 11857752, 17426081, 16199547, 10712197, 23913538, 28492532
SCV000588827	Medical Genetics, University of Parma	no assertion criteria provided	Likely pathogenic (Feb 2, 2017)	germline	clinical testing
SCV000692364	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	no assertion criteria provided	Pathogenic (Dec 13, 2016)	germline	clinical testing
SCV001499693	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 2, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002560221	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 15, 2022)	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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1.

Ars E, Serra E, García J, Kruyer H, Gaona A, Lázaro C, Estivill X.

Hum Mol Genet. 2000 Jan 22;9(2):237-47. Erratum in: Hum Mol Genet 2000 Mar 1;9(4):659.

PubMed [citation]

PMID:: 10607834

Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 ( NF1) gene.

Han SS, Cooper DN, Upadhyaya MN.

Hum Genet. 2001 Nov;109(5):487-97. Epub 2001 Oct 11.

PubMed [citation]

PMID:: 11735023

See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000542170.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 10607834, 11735023, 11857752, 17426081). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 45 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). ClinVar contains an entry for this variant (Variation ID: 404571). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

#	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

From Medical Genetics, University of Parma, SCV000588827.1

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

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

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV000692364.1

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

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

From Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SCV001499693.1

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

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

From Genome-Nilou Lab, SCV002560221.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine