NM_006118.4(HAX1):c.125G>A (p.Gly42Asp) AND Kostmann syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 14, 2019
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:: RCV001244336.10

Allele description [Variation Report for NM_006118.4(HAX1):c.125G>A (p.Gly42Asp)]

NM_006118.4(HAX1):c.125G>A (p.Gly42Asp)

Gene:

HAX1:HCLS1 associated protein X-1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_006118.4(HAX1):c.125G>A (p.Gly42Asp)

HGVS:

NC_000001.11:g.154273407G>A
NG_007369.1:g.5845G>A
NM_001018837.2:c.54-73G>A
NM_006118.4:c.125G>AMANE SELECT
NP_006109.2:p.Gly42Asp
LRG_64t1:c.125G>A
LRG_64:g.5845G>A
NC_000001.10:g.154245883G>A
NM_006118.3:c.125G>A

Protein change:

G42D

Links:

dbSNP: rs1001600867

NCBI 1000 Genomes Browser:

rs1001600867

Molecular consequence:

NM_001018837.2:c.54-73G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_006118.4:c.125G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001417548	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002085817	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 15, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001417548

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 14, 2019)

germline

clinical testing

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

SCV002085817

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 15, 2021)

germline

clinical testing

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001417548.5

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

Description

This sequence change replaces glycine with aspartic acid at codon 42 of the HAX1 protein (p.Gly42Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HAX1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.

#	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

From Natera, Inc., SCV002085817.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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: Sep 29, 2024

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