rs17326758

chrX-118641602-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144658.4(DOCK11):c.4260+297T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 111,183 control chromosomes in the GnomAD database, including 477 homozygotes. There are 3,308 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.098 (477 hom., 3308 hem., cov: 22)
• Consequence: DOCK11 NM_144658.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK11	NM_144658.4	c.4260+297T>G		intron_variant		ENST00000276202.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK11	ENST00000276202.9	c.4260+297T>G		intron_variant		1	NM_144658.4	P4
DOCK11	ENST00000276204.10	c.4260+297T>G		intron_variant		5		A1
DOCK11	ENST00000633080.1	c.3747+297T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 10900 AN: 111127 Hom.: 478 Cov.: 22 AF XY: 0.0992 AC XY: 3305 AN XY: 33311

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0794

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0980 AC: 10901 AN: 111183 Hom.: 477 Cov.: 22 AF XY: 0.0991 AC XY: 3308 AN XY: 33377

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0794

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.111

Alfa AF: 0.124 Hom.: 2377

Bravo AF: 0.0934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.1
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs17326758; hg19: chrX-117775565;