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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 8, 2024
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:: RCV002315794.9

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:: 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

Recent activity

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excinuclease ABC subunit UvrB [Roseibacillus persicicus]
excinuclease ABC subunit UvrB [Roseibacillus persicicus]
gi|2573598056|ref|WP_308428515.1|

Protein
YhaN family protein [Roseibacillus persicicus]
YhaN family protein [Roseibacillus persicicus]
gi|2815298332|ref|WP_377047555.1|

Protein
thioesterase family protein [Roseibacillus persicicus]
thioesterase family protein [Roseibacillus persicicus]
gi|2815298421|ref|WP_377047643.1|

Protein
Pluteus aff. salicinus UBC F28390 18S ribosomal RNA gene, partial sequence; inte...
Pluteus aff. salicinus UBC F28390 18S ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S ribosomal RNA gene, partial sequence
gi|828345538|gb|KP454021.1|

Nucleotide
Saccharomyces cerevisiae strain EM14S01-3B genome assembly, chromosome: 9
Saccharomyces cerevisiae strain EM14S01-3B genome assembly, chromosome: 9
gi|1932821368|emb|LR813559.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000663248	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 8, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000663248

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 8, 2024)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV000663248.5

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

Description

The c.4_5delGCinsTT variant (also known as p.A2F), located in coding exon 1 of the NF1 gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 4 to 5. This results in the substitution of the alanine residue for a phenylalanine residue at codon 2, an amino acid with dissimilar properties. This variant has been detected in the homozygous state in a 66-year-old individual with no reported features of neurofibromatosis type 1 (Ambry internal data). This amino acid position is well conserved on limited sequence alignment. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this alteration remains unclear.

#	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: Nov 3, 2024

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