NM_203447.4(DOCK8):c.1783A>G (p.Ser595Gly) AND Combined immunodeficiency due to DOCK8 deficiency

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 2021
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:: RCV000685647.10

Allele description

NM_203447.4(DOCK8):c.1783A>G (p.Ser595Gly)

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.1783A>G (p.Ser595Gly)

HGVS:

NC_000009.12:g.368121A>G
NG_017007.1:g.158257A>G
NM_001190458.2:c.1579A>G
NM_001193536.2:c.1579A>G
NM_203447.4:c.1783A>GMANE SELECT
NP_001177387.1:p.Ser527Gly
NP_001180465.1:p.Ser527Gly
NP_982272.2:p.Ser595Gly
NP_982272.2:p.Ser595Gly
LRG_196t1:c.1783A>G
LRG_196:g.158257A>G
LRG_196p1:p.Ser595Gly
NC_000009.11:g.368121A>G
NM_203447.3:c.1783A>G

Protein change:

S527G

Links:

dbSNP: rs974346101

NCBI 1000 Genomes Browser:

rs974346101

Molecular consequence:

NM_001190458.2:c.1579A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001193536.2:c.1579A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_203447.4:c.1783A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000813135	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2021)	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

SCV000813135

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2021)

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	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000813135.6

#	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 serine with glycine at codon 595 of the DOCK8 protein (p.Ser595Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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: Oct 21, 2023

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