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NM_001042492.3(NF1):c.2540T>C (p.Leu847Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 16, 2015
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:
RCV000492608.2

Allele description [Variation Report for NM_001042492.3(NF1):c.2540T>C (p.Leu847Pro)]

NM_001042492.3(NF1):c.2540T>C (p.Leu847Pro)

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.2540T>C (p.Leu847Pro)
HGVS:
  • NC_000017.11:g.31229155T>C
  • NG_009018.1:g.139179T>C
  • NM_000267.3:c.2540T>C
  • NM_001042492.3:c.2540T>CMANE SELECT
  • NP_000258.1:p.Leu847Pro
  • NP_001035957.1:p.Leu847Pro
  • NP_001035957.1:p.Leu847Pro
  • LRG_214t1:c.2540T>C
  • LRG_214t2:c.2540T>C
  • LRG_214:g.139179T>C
  • LRG_214p1:p.Leu847Pro
  • LRG_214p2:p.Leu847Pro
  • NC_000017.10:g.29556173T>C
  • NM_001042492.2:c.2540T>C
  • NM_001042492.3:c.2540T>C
  • P21359:p.Leu847Pro
Protein change:
L847P
Links:
UniProtKB: P21359#VAR_021748; UniProtKB/Swiss-Prot: VAR_021748; dbSNP: rs199474747
NCBI 1000 Genomes Browser:
rs199474747
Molecular consequence:
  • NM_000267.3:c.2540T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042492.3:c.2540T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000581250Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))		Likely pathogenic
(Apr 16, 2015) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical 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

Molecular diagnosis of neurofibromatosis type 1: 2 years experience.

Griffiths S, Thompson P, Frayling I, Upadhyaya M.

Fam Cancer. 2007;6(1):21-34.

PubMed [citation]
PMID:
16944272
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000581250.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The p.L847P variant (also known as c.2540T>C), located in coding exon 21 of the NF1 gene, results from a T to C substitution at nucleotide position 2540. The leucine at codon 847 is replaced by proline, an amino acid with similar properties. This variant has been described in multiple cohorts of NF1 patients (<span style="background-color:initial">Fahsold R et al.Am. J. Hum. Genet. 2000 Mar; 66(3):790-818, Griffiths S et al. Fam. Cancer 2007; 6(1):21-34, Ko JM et al. Pediatr. Neurol. 2013 Jun; 48(6):447-53, Nemethova M et al. Ann. Hum. Genet. 2013 Sep; 77(5):364-79)<span style="background-color:initial">.<span style="background-color:initial">This variant was previously reported in the SNPDatabase as rs199474747 but<span style="background-color:initial">was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 55,000 alleles tested) in our clinical cohort.<span style="background-color:initial">This amino acid position is highly conserved on sequence alignment of available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.<span style="background-color:initial">Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Dec 14, 2024