NM_001972.4(ELANE):c.251T>C (p.Leu84Pro) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 2022
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:: RCV001796069.15

Allele description [Variation Report for NM_001972.4(ELANE):c.251T>C (p.Leu84Pro)]

NM_001972.4(ELANE):c.251T>C (p.Leu84Pro)

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.251T>C (p.Leu84Pro)

HGVS:

NC_000019.10:g.853288T>C
NG_009627.1:g.5998T>C
NM_001972.3:c.251T>C
NM_001972.4:c.251T>CMANE SELECT
NP_001963.1:p.Leu84Pro
LRG_57t1:c.251T>C
LRG_57:g.5998T>C
NC_000019.9:g.853288T>C
NM_001972.2:c.251T>C

Protein change:

L84P

Links:

dbSNP: rs1064793108

NCBI 1000 Genomes Browser:

rs1064793108

Molecular consequence:

NM_001972.4:c.251T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001226661	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14962902, 23463630, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001226661

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2022)

germline

clinical testing

PubMed (3)
[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

Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register.

Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J.

Blood. 2004 Jun 1;103(11):4119-25. Epub 2004 Feb 12.

PubMed [citation]

PMID:: 14962902

The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia.

Germeshausen M, Deerberg S, Peter Y, Reimer C, Kratz CP, Ballmaier M.

Hum Mutat. 2013 Jun;34(6):905-14. doi: 10.1002/humu.22308. Epub 2013 Apr 2.

PubMed [citation]

PMID:: 23463630

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001226661.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 418179). This variant is also known as g.2199T>C and Leu55Pro. This missense change has been observed in individual(s) with congenital neutropenia (PMID: 14962902, 23463630; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 84 of the ELANE protein (p.Leu84Pro).

#	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: Oct 26, 2024

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