NM_001972.4(ELANE):c.569T>G (p.Val190Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 23, 2020
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:: RCV001796467.15

Allele description [Variation Report for NM_001972.4(ELANE):c.569T>G (p.Val190Gly)]

NM_001972.4(ELANE):c.569T>G (p.Val190Gly)

Gene:

ELANE:elastase, neutrophil expressed [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_001972.4(ELANE):c.569T>G (p.Val190Gly)

HGVS:

NC_000019.10:g.855766T>G
NG_007274.1:g.1102T>G
NG_009627.1:g.8476T>G
NM_001972.2:c.569T>G
NM_001972.4:c.569T>GMANE SELECT
NP_001963.1:p.Val190Gly
LRG_57t1:c.569T>G
LRG_46:g.1102T>G
LRG_57:g.8476T>G
NC_000019.9:g.855766T>G

Protein change:

V190G

Links:

dbSNP: rs1322572531

NCBI 1000 Genomes Browser:

rs1322572531

Molecular consequence:

NM_001972.4:c.569T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cyclical neutropenia
Synonyms:: Cyclic hematopoiesis
Identifiers:: MONDO: MONDO:0008090; MedGen: C0221023; Orphanet: 2686; OMIM: 162800; Human Phenotype Ontology: HP:0040289

Name:: Neutropenia, severe congenital, 1, autosomal dominant
Identifiers:: MONDO: MONDO:0042490; MedGen: C1859966; OMIM: 202700

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uncharacterized protein C2orf80 homolog isoform X1 [Pan troglodytes]
uncharacterized protein C2orf80 homolog isoform X1 [Pan troglodytes]
gi|2468617718|ref|XP_054535237.1|

Protein
hydroxyacylglutathione hydrolase-like protein isoform 2 [Homo sapiens]
hydroxyacylglutathione hydrolase-like protein isoform 2 [Homo sapiens]
gi|588480498|ref|NP_001277068.1|

Protein
Homologene neighbors for GEO Profiles (Select 125866640) (0)
GEO Profiles
Profile neighbors for GEO Profiles (Select 132378427) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 125866307) (20)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001567692	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2020)	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

SCV001567692

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2020)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001567692.4

#	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 valine with glycine at codon 190 of the ELANE protein (p.Val190Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ELANE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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

Last Updated: Nov 3, 2024

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