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NM_001042492.3(NF1):c.4_5delinsTT (p.Ala2Phe) AND Neurofibromatosis, type 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 21, 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:
RCV000632482.13

Allele description [Variation Report for NM_001042492.3(NF1):c.4_5delinsTT (p.Ala2Phe)]

NM_001042492.3(NF1):c.4_5delinsTT (p.Ala2Phe)

Genes:
MIR4733HG:MIR4733 host gene [Gene - HGNC]
LOC111811965:NF1 (neurofibromin 1) promoter region [Gene]
NF1:neurofibromin 1 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
17q11.2
Genomic location:
Preferred name:
NM_001042492.3(NF1):c.4_5delinsTT (p.Ala2Phe)
HGVS:
  • NC_000017.11:g.31095313_31095314delinsTT
  • NG_009018.1:g.5337_5338delinsTT
  • NG_056197.1:g.1809_1810delinsTT
  • NM_000267.3:c.4_5delinsTT
  • NM_001042492.3:c.4_5delinsTTMANE SELECT
  • NM_001128147.3:c.4_5delinsTT
  • NP_000258.1:p.Ala2Phe
  • NP_001035957.1:p.Ala2Phe
  • NP_001121619.1:p.Ala2Phe
  • LRG_214t1:c.4_5delinsTT
  • LRG_214:g.5337_5338delinsTT
  • LRG_214p1:p.Ala2Phe
  • NC_000017.10:g.29422331_29422332delinsTT
  • NM_000267.3:c.4_5delGCinsTT
  • NM_000267.3:c.4_5delinsTT
Protein change:
A2F
Links:
dbSNP: rs1555594471
NCBI 1000 Genomes Browser:
rs1555594471
Molecular consequence:
  • NM_000267.3:c.4_5delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042492.3:c.4_5delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128147.3:c.4_5delinsTT - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000753667Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 21, 2023) 		germlineclinical testing

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

SCV002561387Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 15, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000753667.3

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2 of the NF1 protein (p.Ala2Phe). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 480205). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV002561387.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024