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NM_203447.4(DOCK8):c.4346C>T (p.Ser1449Leu) AND DOCK8-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 28, 2023
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:
RCV003392247.4

Allele description [Variation Report for NM_203447.4(DOCK8):c.4346C>T (p.Ser1449Leu)]

NM_203447.4(DOCK8):c.4346C>T (p.Ser1449Leu)

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.4346C>T (p.Ser1449Leu)
HGVS:
  • NC_000009.12:g.428369C>T
  • NG_017007.1:g.218505C>T
  • NM_001190458.2:c.4046C>T
  • NM_001193536.2:c.4142C>T
  • NM_203447.4:c.4346C>TMANE SELECT
  • NP_001177387.1:p.Ser1349Leu
  • NP_001180465.1:p.Ser1381Leu
  • NP_982272.2:p.Ser1449Leu
  • NP_982272.2:p.Ser1449Leu
  • LRG_196t1:c.4346C>T
  • LRG_196:g.218505C>T
  • LRG_196p1:p.Ser1449Leu
  • NC_000009.11:g.428369C>T
  • NM_203447.3:c.4346C>T
Protein change:
S1349L
Links:
dbSNP: rs370123223
NCBI 1000 Genomes Browser:
rs370123223
Molecular consequence:
  • NM_001190458.2:c.4046C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193536.2:c.4142C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_203447.4:c.4346C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
DOCK8-related disorder
Synonyms:
DOCK8-related condition
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004110949PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Apr 28, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 PreventionGenetics, part of Exact Sciences, SCV004110949.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The DOCK8 c.4346C>T variant is predicted to result in the amino acid substitution p.Ser1449Leu. This variant has been reported in the homozygous state in three related Saudi patients from a highly consanguineous family (Al Shekaili et al. 2017. PubMed ID: 27890707). Of note, these individuals were also homozygous for a splicing variant, c.4626+5G>A, in DOCK8 that was predicted to impact splicing based on splicing predication programs and abolish protein product via western blot analysis (Alamut Visual Plus v1.6.1; Al Shekaili et al. 2017. PubMed ID: 27890707). This variant was also reported in the compound heterozygous state in an individual with suspected primary immunodeficiency (Table E2 - Platt et al. 2021. PubMed ID: 32888943). This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-428369-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 29, 2024