NM_203447.4(DOCK8):c.1357G>T (p.Glu453Ter) AND Combined immunodeficiency due to DOCK8 deficiency

Germline classification:: Pathogenic (1 submission)
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:: RCV003335887.1

Allele description [Variation Report for NM_203447.4(DOCK8):c.1357G>T (p.Glu453Ter)]

NM_203447.4(DOCK8):c.1357G>T (p.Glu453Ter)

Gene:

DOCK8:dedicator of cytokinesis 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p24.3

Genomic location:

Preferred name:

NM_203447.4(DOCK8):c.1357G>T (p.Glu453Ter)

HGVS:

NC_000009.12:g.336653G>T
NG_017007.1:g.126789G>T
NM_001190458.2:c.1153G>T
NM_001193536.2:c.1153G>T
NM_203447.4:c.1357G>TMANE SELECT
NP_001177387.1:p.Glu385Ter
NP_001180465.1:p.Glu385Ter
NP_982272.2:p.Glu453Ter
NP_982272.2:p.Glu453Ter
LRG_196t1:c.1357G>T
LRG_196:g.126789G>T
LRG_196p1:p.Glu453Ter
NC_000009.11:g.336653G>T
NM_203447.3:c.1357G>T

Protein change:

E385*

Molecular consequence:

NM_001190458.2:c.1153G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001193536.2:c.1153G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_203447.4:c.1357G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Combined immunodeficiency due to DOCK8 deficiency (HIES2)
Synonyms:: HIES autosomal recessive; Hyper-IgE recurrent infection syndrome, autosomal recessive; HYPER-IgE RECURRENT INFECTION SYNDROME 2, AUTOSOMAL RECESSIVE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009478; MedGen: C4722305; Orphanet: 217390; OMIM: 243700

Recent activity

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bifunctional proline dehydrogenase/L-glutamate gamma-semialdehyde dehydrogenase ...
bifunctional proline dehydrogenase/L-glutamate gamma-semialdehyde dehydrogenase PutA [Dechloromonas agitata]
gi|653253266|ref|WP_027458672.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046126	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004046126

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046126.1

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

Description

This nonsense variant found in exon 12 of 48 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as homozygous change in patients with DOCK8 deficiency (alternative nomenclature using NM_203447.3: c.1153G>T (p.Glu385Ter), PMID: 19776401). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0004% (1/251374) and thus is presumed to be rare. Based on the available evidence, the c.1357G>T (p.Glu453Ter) variant is classified as Pathogenic.

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

Last Updated: Jun 29, 2024

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