chr8-25410106-A-G

Variant names:

• chr8-25410106-A-G
• rs2709618
• NM_024940.8:c.5412A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024940.8(DOCK5):​c.5412A>G​(p.Pro1804Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,610,598 control chromosomes in the GnomAD database, including 305,203 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 0.53 (23361 hom., cov: 29)
  • Exomes 𝑓: 0.62 (281842 hom.)
• Consequence: DOCK5 NM_024940.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 26 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.212 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024940.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK5	NM_024940.8	MANE Select	c.5412A>G	p.Pro1804Pro	synonymous	Exon 51 of 52	NP_079216.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK5	ENST00000276440.12	TSL:1 MANE Select	c.5412A>G	p.Pro1804Pro	synonymous	Exon 51 of 52	ENSP00000276440.7
	DOCK5	ENST00000467709.6	TSL:5	n.*3270A>G		non_coding_transcript_exon	Exon 35 of 36	ENSP00000428479.1
	DOCK5	ENST00000479547.2	TSL:5	n.110A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81044 AN: 151502 Hom.: 23357 Cov.: 29

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.572

GnomAD2 exomes AF: 0.599 AC: 149025 AN: 248840 AF XY: 0.604

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.619

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.613

GnomAD4 exome AF: 0.619 AC: 902628 AN: 1458976 Hom.: 281842 Cov.: 38 AF XY: 0.619 AC XY: 449593 AN XY: 725758

African (AFR) AF: 0.284 AC: 9511 AN: 33460

American (AMR) AF: 0.615 AC: 27378 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 16229 AN: 26088

East Asian (EAS) AF: 0.639 AC: 25324 AN: 39634

South Asian (SAS) AF: 0.608 AC: 52359 AN: 86052

European-Finnish (FIN) AF: 0.636 AC: 33894 AN: 53318

Middle Eastern (MID) AF: 0.601 AC: 3465 AN: 5768

European-Non Finnish (NFE) AF: 0.629 AC: 697659 AN: 1109880

Other (OTH) AF: 0.611 AC: 36809 AN: 60262

GnomAD4 genome AF: 0.535 AC: 81070 AN: 151622 Hom.: 23361 Cov.: 29 AF XY: 0.539 AC XY: 39910 AN XY: 74006

African (AFR) AF: 0.295 AC: 12185 AN: 41332

American (AMR) AF: 0.600 AC: 9140 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2208 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3228 AN: 5054

South Asian (SAS) AF: 0.595 AC: 2861 AN: 4812

European-Finnish (FIN) AF: 0.644 AC: 6753 AN: 10488

Middle Eastern (MID) AF: 0.642 AC: 185 AN: 288

European-Non Finnish (NFE) AF: 0.630 AC: 42770 AN: 67924

Other (OTH) AF: 0.570 AC: 1200 AN: 2104

Alfa AF: 0.600 Hom.: 40789

Bravo AF: 0.520

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.37
DANN	Benign	0.51
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs2709618; hg19: chr8-25267622; COSMIC: COSV52396129;