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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 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:: RCV001796472.12

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

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

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>T

HGVS:

NC_000019.10:g.855799G>T
NG_007274.1:g.1135G>T
NG_009627.1:g.8509G>T
NM_001972.4:c.597+5G>TMANE SELECT
LRG_46:g.1135G>T
LRG_57:g.8509G>T
NC_000019.9:g.855799G>T

Links:

dbSNP: rs879253882

NCBI 1000 Genomes Browser:

rs879253882

Molecular consequence:

NM_001972.4:c.597+5G>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001579959	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 23, 2020)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17576681, 9536098, 25912133, 10581030, 23463630, 20049848, 30040071, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001579959

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 23, 2020)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001579959.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

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, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with cyclic neutropenia (PMID: 23463630, 25912133). It has also been observed to segregate with disease in related individuals. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 23463630, 25912133). This variant disrupts the c.597+5G nucleotide in the ELANE gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 10581030, 23463630, 20049848, 30040071). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 20, 2024

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