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

Recent activity

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sulfatase [Roseibacillus persicicus]
sulfatase [Roseibacillus persicicus]
gi|2403466550|ref|WP_268244904.1|

Protein
CRISPR-associated endonuclease Cas2 [Roseibacillus persicicus]
CRISPR-associated endonuclease Cas2 [Roseibacillus persicicus]
gi|2155109621|ref|WP_229809590.1|

Protein
Saccharomyces cerevisiae strain EM14S01-3B genome assembly, chromosome: 10
Saccharomyces cerevisiae strain EM14S01-3B genome assembly, chromosome: 10
gi|1932821750|emb|LR813560.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000753667	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 21, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002561387	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000753667

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 21, 2023)

germline

clinical testing

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

SCV002561387

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 15, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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

From Genome-Nilou Lab, SCV002561387.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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