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NM_001042492.3(NF1):c.288+4A>T AND Neurofibromatosis, type 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 2, 2022
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:
RCV002272972.4

Allele description [Variation Report for NM_001042492.3(NF1):c.288+4A>T]

NM_001042492.3(NF1):c.288+4A>T

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.288+4A>T
HGVS:
  • NC_000017.11:g.31159097A>T
  • NG_009018.1:g.69121A>T
  • NM_000267.3:c.288+4A>T
  • NM_001042492.3:c.288+4A>TMANE SELECT
  • NM_001128147.3:c.288+4A>T
  • LRG_214t1:c.288+4A>T
  • LRG_214t2:c.288+4A>T
  • LRG_214:g.69121A>T
  • NC_000017.10:g.29486115A>T
  • NM_001042492.2:c.288+4A>T
Links:
dbSNP: rs781459468
NCBI 1000 Genomes Browser:
rs781459468
Molecular consequence:
  • NM_000267.3:c.288+4A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001042492.3:c.288+4A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001128147.3:c.288+4A>T - intron variant - [Sequence Ontology: SO:0001627]

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002557478Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Sep 2, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Neurofibromatosis 1.

Friedman JM.

1998 Oct 2 [updated 2022 Apr 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]
PMID:
20301288

Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders.

Giugliano T, Santoro C, Torella A, Del Vecchio Blanco F, Grandone A, Onore ME, Melone MAB, Straccia G, Melis D, Piccolo V, Limongelli G, Buono S, Perrotta S, Nigro V, Piluso G.

Genes (Basel). 2019 Jul 31;10(8). doi:pii: E580. 10.3390/genes10080580.

PubMed [citation]
PMID:
31370276
PMCID:
PMC6722641
See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557478.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with neurofibromatosis, type 1 (MIM#162200). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 20301288). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0311 - An alternative nucleotide change at the same position is present in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0508 - In silico predictions for abnormal splicing are conflicting. (I) 0704 - Another splice site variant comparable to the one identified in this case has limited previous evidence for pathogenicity. c.288+4A>G has been classified as likely pathogenic, pathogenic and as a VUS by clinical laboratories in ClinVar. This alternative change has also been observed in one individual with an NF1-related condition in the literature (PMID: 31370276). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Jul 23, 2024