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NM_020812.4(DOCK6):c.5939+2T>C AND not provided

Germline classification:
Pathogenic (4 submissions)
Last evaluated:
Oct 14, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001242778.10

Allele description [Variation Report for NM_020812.4(DOCK6):c.5939+2T>C]

NM_020812.4(DOCK6):c.5939+2T>C

Gene:
DOCK6:dedicator of cytokinesis 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_020812.4(DOCK6):c.5939+2T>C
HGVS:
  • NC_000019.10:g.11200714A>G
  • NG_031953.1:g.66779T>C
  • NG_051186.1:g.1854T>C
  • NG_051186.2:g.2151T>C
  • NM_001367830.1:c.6044+2T>C
  • NM_020812.4:c.5939+2T>CMANE SELECT
  • NC_000019.9:g.11311390A>G
  • NM_020812.2:c.5939+2T>C
  • NM_020812.3:c.5939+2T>C
Nucleotide change:
IVS46DS, +2, T-C
Links:
OMIM: 614194.0006; dbSNP: rs201387914
NCBI 1000 Genomes Browser:
rs201387914
Molecular consequence:
  • NM_001367830.1:c.6044+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_020812.4:c.5939+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001415887Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Oct 14, 2023)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001817220GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Pathogenic
(Feb 16, 2022)
germlineclinical testing

Citation Link,

SCV001978647Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus
no assertion criteria provided
Pathogenicgermlineclinical testing

SCV001980096Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Likely pathogenicgermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome.

Shaheen R, Faqeih E, Sunker A, Morsy H, Al-Sheddi T, Shamseldin HE, Adly N, Hashem M, Alkuraya FS.

Am J Hum Genet. 2011 Aug 12;89(2):328-33. doi: 10.1016/j.ajhg.2011.07.009. Epub 2011 Aug 4.

PubMed [citation]
PMID:
21820096
PMCID:
PMC3155174
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001415887.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change affects a donor splice site in intron 46 of the DOCK6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DOCK6 are known to be pathogenic (PMID: 21820096, 25824905). This variant is present in population databases (rs201387914, gnomAD 0.04%). Disruption of this splice site has been observed in individual(s) with Aicardi-GoutieÃÄres syndrome and Adams-Oliver syndrome (PMID: 25824905, 28884918, 30111349). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 253047). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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

From GeneDx, SCV001817220.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25824905, 30111349, 31654484, 29961505, 29924900, 31589614, 28884918)

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001978647.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001980096.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024