NM_001042492.3(NF1):c.7155_7158dup (p.Asn2387delinsLeuTer) AND Neurofibromatosis, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 3, 2023
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:: RCV003597539.2

Allele description [Variation Report for NM_001042492.3(NF1):c.7155_7158dup (p.Asn2387delinsLeuTer)]

NM_001042492.3(NF1):c.7155_7158dup (p.Asn2387delinsLeuTer)

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.7155_7158dup (p.Asn2387delinsLeuTer)

HGVS:

NC_000017.11:g.31343101_31343104dup
NG_009018.1:g.253125_253128dup
NM_000267.3:c.7092_7095dup
NM_001042492.3:c.7155_7158dupMANE SELECT
NP_000258.1:p.Asn2366delinsLeuTer
NP_001035957.1:p.Asn2387Leufs
NP_001035957.1:p.Asn2387delinsLeuTer
LRG_214t1:c.7092_7095dup
LRG_214t2:c.7155_7158dup
LRG_214:g.253125_253128dup
LRG_214p1:p.Asn2366delinsLeuTer
LRG_214p2:p.Asn2387Leufs
NC_000017.10:g.29670118_29670119insCTTT
NC_000017.10:g.29670119_29670122dup
NM_001042492.2:c.7155_7158dup

Molecular consequence:

NM_000267.3:c.7092_7095dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001042492.3:c.7155_7158dup - nonsense - [Sequence Ontology: SO:0001587]

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

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Homo sapiens TBC1 domain family member 13 (TBC1D13), transcript variant 1, mRNA
Homo sapiens TBC1 domain family member 13 (TBC1D13), transcript variant 1, mRNA
gi|1519312758|ref|NM_018201.5|

Nucleotide
Homologene neighbors for GEO Profiles (Select 132534351) (0)
GEO Profiles
Profile neighbors for GEO Profiles (Select 132571816) (67)
GEO Profiles
IKZF2 IKAROS family zinc finger 2 [Homo sapiens]
IKZF2 IKAROS family zinc finger 2 [Homo sapiens]
Gene ID:22807

Gene
Gene Links for GEO Profiles (Select 132560700) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004461005	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10712197, 23913538, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004461005

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 3, 2023)

germline

clinical testing

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

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

Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain.

Fahsold R, Hoffmeyer S, Mischung C, Gille C, Ehlers C, Kücükceylan N, Abdel-Nour M, Gewies A, Peters H, Kaufmann D, Buske A, Tinschert S, Nürnberg P.

Am J Hum Genet. 2000 Mar;66(3):790-818.

PubMed [citation]

PMID:: 10712197
PMCID:: PMC1288164

NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: the French experience.

Sabbagh A, Pasmant E, Imbard A, Luscan A, Soares M, Blanché H, Laurendeau I, Ferkal S, Vidaud M, Pinson S, Bellanné-Chantelot C, Vidaud D, Parfait B, Wolkenstein P.

Hum Mutat. 2013 Nov;34(11):1510-8. doi: 10.1002/humu.22392. Epub 2013 Aug 26.

PubMed [citation]

PMID:: 23913538

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004461005.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn2366Leufs*2) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538).

#	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: Sep 29, 2024

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