X-118496045-C-CT

Position:

• chrX-118496045-C-CT

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_144658.4(DOCK11):​c.75dupT​(p.Glu26fs) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: DOCK11 NM_144658.4 frameshift, stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.231

Genes affected

DOCK11 (HGNC:23483): (dedicator of cytokinesis 11) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including marginal zone B cell differentiation; positive regulation of GTPase activity; and positive regulation of filopodium assembly. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.988 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-118496045-C-CT is Pathogenic according to our data. Variant chrX-118496045-C-CT is described in ClinVar as [Pathogenic]. Clinvar id is 2444466.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4	c.75dupT	p.Glu26fs	frameshift_variant, stop_gained	1/53	ENST00000276202.9	NP_653259.3
DOCK11	XM_005262368.5	c.75dupT	p.Glu26fs	frameshift_variant, stop_gained	1/54		XP_005262425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK11	ENST00000276202.9	c.75dupT	p.Glu26fs	frameshift_variant, stop_gained	1/53	1	NM_144658.4	ENSP00000276202.7
DOCK11	ENST00000276204.10	c.75dupT	p.Glu26fs	frameshift_variant, stop_gained	1/53	5		ENSP00000276204.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Autoinflammatory disease, multisystem, with immune dysregulation, X-linked Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 12, 2023

- -

Inborn error of hematopoiesis and immunity with systemic inflammation and normocytic anemia Pathogenic:1

Pathogenic, criteria provided, single submitter

research

St. Anna Children's Cancer Research Institute (CCRI)

Mar 15, 2023

Null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease. Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product. Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or ExAC. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-117630008;