9-451977-ATTTTTTTTTTTTTTTTT-A

Variant names:

• chr9-451977-ATTTTTTTTTTTTTTTTT-A
• rs35071801
• NM_203447.4:c.5962-25_5962-9delTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_203447.4(DOCK8):​c.5962-25_5962-9delTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOCK8 NM_203447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 1 publications found

Genes affected

DOCK8 (HGNC:19191): (dedicator of cytokinesis 8) This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

DOCK8 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to DOCK8 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK8	NM_203447.4	c.5962-25_5962-9delTTTTTTTTTTTTTTTTT		intron_variant	Intron 45 of 47	ENST00000432829.7	NP_982272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7	c.5962-33_5962-17delTTTTTTTTTTTTTTTTT		intron_variant	Intron 45 of 47	1	NM_203447.4	ENSP00000394888.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000394 AC: 4 AN: 101472 Hom.: 0 AF XY: 0.0000655 AC XY: 4 AN XY: 61032

African (AFR) AF: 0.00 AC: 0 AN: 1488

American (AMR) AF: 0.00 AC: 0 AN: 4190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2708

East Asian (EAS) AF: 0.00 AC: 0 AN: 5036

South Asian (SAS) AF: 0.000471 AC: 4 AN: 8496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 356

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 70148

Other (OTH) AF: 0.00 AC: 0 AN: 4978

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
La Branchor		0.26
BranchPoint Hunter		4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35071801; hg19: chr9-451977;