NM_000433.4(NCF2):c.1340C>T (p.Ala447Val) AND Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 11, 2021
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:: RCV001968790.5

Allele description [Variation Report for NM_000433.4(NCF2):c.1340C>T (p.Ala447Val)]

NM_000433.4(NCF2):c.1340C>T (p.Ala447Val)

Gene:

NCF2:neutrophil cytosolic factor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q25.3

Genomic location:

Preferred name:

NM_000433.4(NCF2):c.1340C>T (p.Ala447Val)

HGVS:

NC_000001.11:g.183560224G>A
NG_007267.1:g.35358C>T
NM_000433.4:c.1340C>TMANE SELECT
NM_001127651.3:c.1340C>T
NM_001190789.2:c.1097C>T
NM_001190794.2:c.1205C>T
NP_000424.2:p.Ala447Val
NP_001121123.1:p.Ala447Val
NP_001177718.1:p.Ala366Val
NP_001177723.1:p.Ala402Val
LRG_88:g.35358C>T
NC_000001.10:g.183529359G>A

Protein change:

A366V

Links:

dbSNP: rs747548282

NCBI 1000 Genomes Browser:

rs747548282

Molecular consequence:

NM_000433.4:c.1340C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127651.3:c.1340C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001190789.2:c.1097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001190794.2:c.1205C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2
Synonyms:: CGD, AUTOSOMAL RECESSIVE CYTOCHROME b-POSITIVE, TYPE II; GRANULOMATOUS DISEASE, CHRONIC, DUE TO NCF2 DEFICIENCY; GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 2
Identifiers:: MONDO: MONDO:0009310; MedGen: C1856245; Orphanet: 379; OMIM: 233710

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002249641	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 11, 2021)	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

SCV002249641

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 11, 2021)

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	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002249641.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NCF2-related conditions. This variant is present in population databases (rs747548282, ExAC 0.009%). This sequence change replaces alanine with valine at codon 447 of the NCF2 protein (p.Ala447Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine.

#	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: Mar 5, 2024

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