8-25410106-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK5	NM_024940.8	c.5412A>G	p.Pro1804Pro	synonymous_variant	Exon 51 of 52	ENST00000276440.12	NP_079216.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK5	ENST00000276440.12	c.5412A>G	p.Pro1804Pro	synonymous_variant	Exon 51 of 52	1	NM_024940.8	ENSP00000276440.7

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

GnomAD3 exomes AF: 0.599 AC: 149025 AN: 248840 Hom.: 45514 AF XY: 0.604 AC XY: 81191 AN XY: 134452

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 SAS exome AF: 0.605

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

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.615

Gnomad4 ASJ exome AF: 0.622

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.636

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.611

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

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.570

Alfa AF: 0.610 Hom.: 33324

Bravo AF: 0.520

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.37
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2709618; hg19: chr8-25267622; COSMIC: COSV52396129;