NM_024940.8:c.43+9408T>G

Variant names:

• chr8-25194359-T-G
• rs11998492
• NM_024940.8:c.43+9408T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024940.8(DOCK5):​c.43+9408T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,010 control chromosomes in the GnomAD database, including 42,711 homozygotes. 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 0.74 (42711 hom., cov: 30)
• Consequence: DOCK5 NM_024940.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 3 publications found

Genes affected

DOCK5 (HGNC:23476): (dedicator of cytokinesis 5) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family act as guanine nucleotide exchange factors for small Rho family G proteins. The protein encoded by this gene is thought to associate with adaptors CRK and CRKL, and function in regulation of intestinal epithelial cell spreading and migration on collagen IV. Similar proteins in mouse and zebrafish also function in myoblast fusion. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK5	NM_024940.8	c.43+9408T>G		intron_variant	Intron 1 of 51	ENST00000276440.12	NP_079216.4
DOCK5	NM_001322810.2	c.43+9408T>G		intron_variant	Intron 1 of 3		NP_001309739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK5	ENST00000276440.12	c.43+9408T>G		intron_variant	Intron 1 of 51	1	NM_024940.8	ENSP00000276440.7
DOCK5	ENST00000481100.5	c.43+9408T>G		intron_variant	Intron 1 of 10	1		ENSP00000429737.1
DOCK5	ENST00000410074.5	c.43+9408T>G		intron_variant	Intron 1 of 3	2		ENSP00000387036.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112509 AN: 151894 Hom.: 42697 Cov.: 30

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.740 AC: 112561 AN: 152010 Hom.: 42711 Cov.: 30 AF XY: 0.740 AC XY: 54964 AN XY: 74324

African (AFR) AF: 0.575 AC: 23803 AN: 41406

American (AMR) AF: 0.806 AC: 12316 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3333 AN: 5156

South Asian (SAS) AF: 0.615 AC: 2964 AN: 4820

European-Finnish (FIN) AF: 0.866 AC: 9154 AN: 10574

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55394 AN: 67984

Other (OTH) AF: 0.725 AC: 1531 AN: 2112

Alfa AF: 0.685 Hom.: 2987

Bravo AF: 0.733

Asia WGS AF: 0.623 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.74
PhyloP100		-0.095
Mutation Taster		=100/0	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: rs11998492; hg19: chr8-25051875;