rs141632093

Variant names:

• chrX-118566065-C-T
• rs141632093
• NM_144658.4:c.754C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_144658.4(DOCK11):​c.754C>T​(p.Leu252Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,208,666 control chromosomes in the GnomAD database, including 6 homozygotes. There are 242 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., 123 hem., cov: 23)
  • Exomes 𝑓: 0.00042 (4 hom. 119 hem.)
• Consequence: DOCK11 NM_144658.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

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]

DOCK11 Gene-Disease associations (from GenCC):

• autoinflammatory disease, multisystem, with immune dysregulation, X-linked

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant X-118566065-C-T is Benign according to our data. Variant chrX-118566065-C-T is described in ClinVar as Benign. ClinVar VariationId is 783908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.59 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00435 (487/112033) while in subpopulation AFR AF = 0.0148 (456/30908). AF 95% confidence interval is 0.0136. There are 2 homozygotes in GnomAd4. There are 123 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144658.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK11	NM_144658.4	MANE Select	c.754C>T	p.Leu252Leu	synonymous	Exon 8 of 53	NP_653259.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK11	ENST00000276202.9	TSL:1 MANE Select	c.754C>T	p.Leu252Leu	synonymous	Exon 8 of 53	ENSP00000276202.7	Q5JSL3
	DOCK11	ENST00000276204.10	TSL:5	c.754C>T	p.Leu252Leu	synonymous	Exon 8 of 53	ENSP00000276204.6	A6NIW2
	DOCK11	ENST00000966546.1		c.754C>T	p.Leu252Leu	synonymous	Exon 8 of 53	ENSP00000636605.1

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 486 AN: 111978 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00465

GnomAD2 exomes AF: 0.00128 AC: 234 AN: 183051 AF XY: 0.000711

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.000513

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000611

Gnomad OTH exome AF: 0.000886

GnomAD4 exome AF: 0.000424 AC: 465 AN: 1096633 Hom.: 4 Cov.: 30 AF XY: 0.000329 AC XY: 119 AN XY: 362049

African (AFR) AF: 0.0146 AC: 385 AN: 26357

American (AMR) AF: 0.000569 AC: 20 AN: 35164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19374

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00 AC: 0 AN: 54036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.000968 AC: 4 AN: 4133

European-Non Finnish (NFE) AF: 0.0000131 AC: 11 AN: 840823

Other (OTH) AF: 0.000978 AC: 45 AN: 46031

GnomAD4 genome AF: 0.00435 AC: 487 AN: 112033 Hom.: 2 Cov.: 23 AF XY: 0.00359 AC XY: 123 AN XY: 34223

African (AFR) AF: 0.0148 AC: 456 AN: 30908

American (AMR) AF: 0.00152 AC: 16 AN: 10537

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3593

South Asian (SAS) AF: 0.000371 AC: 1 AN: 2695

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6049

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 53175

Other (OTH) AF: 0.00460 AC: 7 AN: 1523

Alfa AF: 0.00174 Hom.: 6

Bravo AF: 0.00511

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.5
DANN	Benign	0.91
PhyloP100		2.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs141632093; hg19: chrX-117700028;