NM_001042492.3(NF1):c.1260+1G>A AND Neurofibromatosis, type 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 30, 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:: RCV000000384.11

Allele description [Variation Report for NM_001042492.3(NF1):c.1260+1G>A]

NM_001042492.3(NF1):c.1260+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.1260+1G>A

HGVS:

NC_000017.11:g.31201486G>A
NG_009018.1:g.111510G>A
NM_000267.3:c.1260+1G>A
NM_001042492.3:c.1260+1G>AMANE SELECT
NM_001128147.3:c.1260+1G>A
LRG_214t1:c.1260+1G>A
LRG_214:g.111510G>A
NC_000017.10:g.29528504G>A
NM_001042492.3:c.1260+1G>A

Nucleotide change:

IVS9DS, G-A, +1

Links:

OMIM: 613113.0025; dbSNP: rs267606603

NCBI 1000 Genomes Browser:

rs267606603

Molecular consequence:

NM_000267.3:c.1260+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001042492.3:c.1260+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001128147.3:c.1260+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
SCV000020528	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2000)	unknown	literature only	PubMed (1) [See all records that cite this PMID]
SCV000542033	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22155606, 10677298, 28492532
SCV002561647	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]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020528

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2000)

unknown

literature only

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

SCV000542033

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 30, 2023)

germline

clinical testing

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

SCV002561647

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	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum and pathogenesis.

Laycock-van Spyk S, Thomas N, Cooper DN, Upadhyaya M.

Hum Genomics. 2011 Oct;5(6):623-90. Review.

PubMed [citation]

PMID:: 22155606
PMCID:: PMC3525246

Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1.

Eisenbarth I, Beyer K, Krone W, Assum G.

Am J Hum Genet. 2000 Feb;66(2):393-401.

PubMed [citation]

PMID:: 10677298
PMCID:: PMC1288091

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000020528.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with type I neurofibromatosis (NF1; 162200), Eisenbarth et al. (2000) identified a germline G-to-A transition at nucleotide 1260+1, the splice donor site of intron 9 of the NF1 gene, leading to the inclusion of 13 bp of intervening sequence into the NF1 messenger. The mutant allele was present in all tissues tested. In a neurofibroma from this patient, an additional C-to-T transition at nucleotide 4021 (Q1341X; 613113.0026), a presumed 'second hit' somatic mutation, was identified. Another neurofibroma from the same patient showed a C-to-T transition at nucleotide 4084 (R1362X; 613113.0027), a presumed further 'second hit' somatic mutation. Both somatic mutations led to premature stop codons in the NF1 message.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000542033.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change affects a donor splice site in intron 11 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10677298, 22155606; Invitae). ClinVar contains an entry for this variant (Variation ID: 356). Studies have shown that disruption of this splice site results in inclusion of 13 base pairs of intronic sequence and introduces a premature termination codon (PMID: 10677298). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, 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

From Genome-Nilou Lab, SCV002561647.1

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine