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NM_001972.4(ELANE):c.597+5G>A AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 6, 2023
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:
RCV001795382.13

Allele description [Variation Report for NM_001972.4(ELANE):c.597+5G>A]

NM_001972.4(ELANE):c.597+5G>A

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.597+5G>A
HGVS:
  • NC_000019.10:g.855799G>A
  • NG_007274.1:g.1135G>A
  • NG_009627.1:g.8509G>A
  • NM_001972.4:c.597+5G>AMANE SELECT
  • LRG_57t1:c.597+5G>A
  • LRG_46:g.1135G>A
  • LRG_57:g.8509G>A
  • NC_000019.9:g.855799G>A
  • NM_001972.2:c.597+5G>A
Nucleotide change:
IVS4DS, G-A, +5
Links:
OMIM: 130130.0005; dbSNP: rs879253882
NCBI 1000 Genomes Browser:
rs879253882
Molecular consequence:
  • NM_001972.4:c.597+5G>A - intron variant - [Sequence Ontology: SO:0001627]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000644191Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 6, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis.

Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC.

Nat Genet. 1999 Dec;23(4):433-6.

PubMed [citation]
PMID:
10581030

Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia.

Malcov M, Reches A, Ben-Yosef D, Cohen T, Amit A, Dgany O, Tamary H, Yaron Y.

Prenat Diagn. 2010 Mar;30(3):207-11. doi: 10.1002/pd.2437.

PubMed [citation]
PMID:
20049848
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000644191.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change falls in intron 4 of the ELANE gene. It does not directly change the encoded amino acid sequence of the ELANE protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with cyclic neutropenia or severe congenital neutropenia (PMID: 10581030, 20049848, 23463630, 30040071). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS4+5G>A. ClinVar contains an entry for this variant (Variation ID: 245598). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of the last 10 residues of exon 4 (Val190-Phe199), but is expected to preserve the integrity of the reading-frame (PMID: 23463630). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 26, 2024