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NM_001042492.3(NF1):c.2446C>T (p.Arg816Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 27, 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:
RCV002311233.8

Allele description [Variation Report for NM_001042492.3(NF1):c.2446C>T (p.Arg816Ter)]

NM_001042492.3(NF1):c.2446C>T (p.Arg816Ter)

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.2446C>T (p.Arg816Ter)
HGVS:
  • NC_000017.11:g.31229061C>T
  • NG_009018.1:g.139085C>T
  • NM_000267.3:c.2446C>T
  • NM_001042492.3:c.2446C>TMANE SELECT
  • NP_000258.1:p.Arg816Ter
  • NP_001035957.1:p.Arg816Ter
  • NP_001035957.1:p.Arg816Ter
  • LRG_214t1:c.2446C>T
  • LRG_214t2:c.2446C>T
  • LRG_214:g.139085C>T
  • LRG_214p1:p.Arg816Ter
  • LRG_214p2:p.Arg816Ter
  • NC_000017.10:g.29556079C>T
  • NM_001042492.2:c.2446C>T
  • NM_001042492.3:c.2446C>T
Protein change:
R816*
Links:
dbSNP: rs886041347
NCBI 1000 Genomes Browser:
rs886041347
Molecular consequence:
  • NM_000267.3:c.2446C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001042492.3:c.2446C>T - nonsense - [Sequence Ontology: SO:0001587]
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
Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000581352Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Jan 27, 2022) 		germlineclinical testing

PubMed (2)
[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

Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types.

Kang E, Kim YM, Seo GH, Oh A, Yoon HM, Ra YS, Kim EK, Kim H, Heo SH, Kim GH, Osborn MJ, Tolar J, Yoo HW, Lee BH.

J Hum Genet. 2020 Jan;65(2):79-89. doi: 10.1038/s10038-019-0695-0. Epub 2019 Nov 28.

PubMed [citation]
PMID:
31776437

Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1.

N Abdel-Aziz N, Y El-Kamah G, A Khairat R, R Mohamed H, Z Gad Y, El-Ghor AM, Amr KS.

Mol Genet Genomic Med. 2021 Dec;9(12):e1631. doi: 10.1002/mgg3.1631. Epub 2021 Jun 3.

PubMed [citation]
PMID:
34080803
PMCID:
PMC8683698

Details of each submission

From Ambry Genetics, SCV000581352.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.R816* variant (also known as c.2446C>T), located in coding exon 21 of the NF1 gene, results from a C to T substitution at nucleotide position 2446. This changes the amino acid from an arginine to a stop codon within coding exon 21. This mutation has been reported multiple times in individuals with clinical features of neurofibromatosis type 1 (Maynard et al. Hum. Genet. 1997; 99:674-76; Bahuau et al. Am J Med Genet. 1998;75(3):265-72; Fahsold et al. Am. J. Hum. Genet. 2000; 66(3):790-818; Jeong et al. J. Korean Med. Sci. 2006;21(1):107-12; Bottillo et al. J. Pathol. 2009; 217(5):693-701; Stenman et al. Endocr. Pathol. 2015; 26(1):9-14; Kang E et al. J Hum Genet, 2020 Jan;65:79-89; N Abdel-Aziz N et al. Mol Genet Genomic Med, 2021 12;9:e1631). This mutation also segregated with disease in ten individuals from one family with neurofibromatosis (Bahuau et al. Am J Med Genet. 1998. 23;75(3):265-72). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Nov 10, 2024