NM_000267.3(NF1):c.6858+1G>A AND Neurofibromatosis, type 1

Clinical significance:Pathogenic (Last evaluated: Oct 14, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000476980.6

Allele description [Variation Report for NM_000267.3(NF1):c.6858+1G>A]

NM_000267.3(NF1):c.6858+1G>A

Gene:
NF1:neurofibromin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q11.2
Genomic location:
Preferred name:
NM_000267.3(NF1):c.6858+1G>A
HGVS:
  • NC_000017.11:g.31338806G>A
  • NG_009018.1:g.248830G>A
  • NM_000267.3:c.6858+1G>A
  • NM_001042492.2:c.6921+1G>A
  • LRG_214t1:c.6858+1G>A
  • LRG_214t2:c.6921+1G>A
  • LRG_214:g.248830G>A
  • NC_000017.10:g.29665824G>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_001042492.2:c.6921+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000542170Invitaecriteria provided, single submitter
Pathogenic
(Oct 14, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV000588827Medical Genetics, University of Parmano assertion criteria providedLikely pathogenic
(Feb 2, 2017)
germlineclinical testing

SCV000692364Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospitalno assertion criteria providedPathogenic
(Dec 13, 2016)
germlineclinical testing

SCV001499693Department of Molecular Diagnostics, Institute of Oncology Ljubljanacriteria provided, single submitter
Pathogenic
(Apr 2, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

NF1 mutations in neurofibromatosis 1 patients with plexiform neurofibromas.

Kluwe L, Friedrich RE, Korf B, Fahsold R, Mautner VF.

Hum Mutat. 2002 Mar;19(3):309.

PubMed [citation]
PMID:
11857752
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000542170.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change affects a donor splice site in intron 45 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individuals affected with neurofibromatosis type 1 (PMID: 11735023, 11857752, 17426081, 10607834). ClinVar contains an entry for this variant (Variation ID: 404571). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Medical Genetics, University of Parma, SCV000588827.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2021

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