NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del) AND Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 25, 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:: RCV000144166.10

Allele description [Variation Report for NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del)]

NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del)

Gene:

JAGN1:jagunal homolog 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del)

HGVS:

NC_000003.12:g.9890757_9890765del
NG_041779.1:g.5171_5179del
NM_001363890.1:c.-234_-226del
NM_032492.4:c.35_43delMANE SELECT
NP_115881.3:p.Thr12_Gly14del
LRG_1228t1:c.35_43del
LRG_1228:g.5171_5179del
LRG_1228p1:p.Thr12_Gly14del
NC_000003.11:g.9932436_9932444del
NC_000003.11:g.9932441_9932449del
NM_032492.3:c.35_43delCCGACGGCA

Links:

OMIM: 616012.0005; dbSNP: rs587777731

NCBI 1000 Genomes Browser:

rs587777731

Molecular consequence:

NM_001363890.1:c.-234_-226del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_032492.4:c.35_43del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency
Synonyms:: Severe congenital neutropenia 6, autosomal recessive
Identifiers:: MONDO: MONDO:0014456; MedGen: C4014954; Orphanet: 423384; OMIM: 616022

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189246	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002130566	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25129144, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189246

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2014)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV002130566

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 25, 2022)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.

Boztug K, Järvinen PM, Salzer E, Racek T, Mönch S, Garncarz W, Gertz EM, Schäffer AA, Antonopoulos A, Haslam SM, Schieck L, Puchałka J, Diestelhorst J, Appaswamy G, Lescoeur B, Giambruno R, Bigenzahn JW, Elling U, Pfeifer D, Conde CD, Albert MH, Welte K, et al.

Nat Genet. 2014 Sep;46(9):1021-7. doi: 10.1038/ng.3069. Epub 2014 Aug 17.

PubMed [citation]

PMID:: 25129144
PMCID:: PMC4829076

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 OMIM, SCV000189246.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 25-year-old German woman with autosomal recessive severe congenital neutropenia-6 (SCN6; 616022), Boztug et al. (2014) identified a homozygous 9-bp deletion (c.35_43del) in exon 1 of the JAGN1 gene, resulting in an in-frame deletion of 3 residues (Thr12_Gly14del). Immunoblot analysis of patient B cells showed decreased expression of a JAGN1 protein variant with a slightly reduced molecular weight. Functional studies of the variant were not performed.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002130566.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.35_43del, results in the deletion of 3 amino acid(s) of the JAGN1 protein (p.Thr12_Gly14del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs752053703, gnomAD 0.002%). This variant has been observed in individual(s) with neutropenia (PMID: 25129144). ClinVar contains an entry for this variant (Variation ID: 156117). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: Feb 14, 2024

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