NC_000001.10:g.(?_153963273)_(154580482_?)del AND Kostmann syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 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:: RCV003116530.4

Allele description

NC_000001.10:g.(?_153963273)_(154580482_?)del

Genes:

ATP8B2:ATPase phospholipid transporting 8B2 [Gene - OMIM - HGNC]
HAX1:HCLS1 associated protein X-1 [Gene - OMIM - HGNC]
SHE:Src homology 2 domain containing E [Gene - OMIM - HGNC]
ADAR:adenosine deaminase RNA specific [Gene - OMIM - HGNC]
AQP10:aquaporin 10 [Gene - OMIM - HGNC]
CHRNB2:cholinergic receptor nicotinic beta 2 subunit [Gene - OMIM - HGNC]
C1orf43:chromosome 1 open reading frame 43 [Gene - OMIM - HGNC]
CFAP141:cilia and flagella associated protein 141 [Gene - HGNC]
IL6R:interleukin 6 receptor [Gene - OMIM - HGNC]
NUP210L:nucleoporin 210 like [Gene - HGNC]
RPS27:ribosomal protein S27 [Gene - OMIM - HGNC]
TPM3:tropomyosin 3 [Gene - OMIM - HGNC]
TDRD10:tudor domain containing 10 [Gene - HGNC]
UBAP2L:ubiquitin associated protein 2 like [Gene - OMIM - HGNC]
UBE2Q1:ubiquitin conjugating enzyme E2 Q1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q21.3

Genomic location:

Chr1: 153963273 - 154580482 (on Assembly GRCh37)

Preferred name:

NC_000001.10:g.(?_153963273)_(154580482_?)del

HGVS:

NC_000001.10:g.(?_153963273)_(154580482_?)del

Condition(s)

Name:: Kostmann syndrome (SCN3)
Synonyms:: Kostmann disease; Agranulocytosis infantile; Autosomal recessive severe congenital neutropenia type 3
Identifiers:: MONDO: MONDO:0012548; MedGen: C5235141; Orphanet: 99749; OMIM: 610738

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003791411	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17187068, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003791411

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease).

Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer AA, Rathinam C, Boztug K, Schwinzer B, Rezaei N, Bohn G, Melin M, Carlsson G, Fadeel B, Dahl N, Palmblad J, Henter JI, Zeidler C, Grimbacher B, Welte K.

Nat Genet. 2007 Jan;39(1):86-92. Epub 2006 Dec 24.

PubMed [citation]

PMID:: 17187068

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 Invitae, SCV003791411.3

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

Description

A gross deletion of the genomic region encompassing the full coding sequence of the HAX1 gene has been identified. Loss-of-function variants in HAX1 are known to be pathogenic (PMID: 17187068). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with HAX1-related conditions. 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: Jun 9, 2024

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