NM_001042492.3(NF1):c.77del (p.Gly26fs) AND Neurofibromatosis, type 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 2021
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:: RCV001916555.3

Allele description

NM_001042492.3(NF1):c.77del (p.Gly26fs)

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.77del (p.Gly26fs)

HGVS:

NC_000017.11:g.31155999del
NG_009018.1:g.66023del
NM_000267.3:c.77del
NM_001042492.3:c.77delMANE SELECT
NM_001128147.3:c.77del
NP_000258.1:p.Gly26fs
NP_001035957.1:p.Gly26fs
NP_001121619.1:p.Gly26fs
LRG_214t1:c.77del
LRG_214:g.66023del
LRG_214p1:p.Gly26fs
NC_000017.10:g.29483016del
NC_000017.10:g.29483017del

Protein change:

G26fs

Links:

dbSNP: rs2143625360

NCBI 1000 Genomes Browser:

rs2143625360

Molecular consequence:

NM_000267.3:c.77del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042492.3:c.77del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128147.3:c.77del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002182405	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 3, 2021)	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

SCV002182405

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 3, 2021)

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 Invitae, SCV002182405.3

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly26Aspfs*18) 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: Feb 28, 2024

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