rs2271108

Positions:

• chr8-25372652-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_024940.8(DOCK5):​c.3618C>T​(p.Asp1206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,609,664 control chromosomes in the GnomAD database, including 187,713 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 0.46 (16465 hom., cov: 32)
  • Exomes 𝑓: 0.48 (171248 hom.)
• Consequence: DOCK5 NM_024940.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK5	NM_024940.8	c.3618C>T	p.Asp1206=	synonymous_variant	35/52	ENST00000276440.12	NP_079216.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK5	ENST00000276440.12	c.3618C>T	p.Asp1206=	synonymous_variant	35/52	1	NM_024940.8	ENSP00000276440	P1
DOCK5	ENST00000444569.5	c.2934C>T	p.Asp978=	synonymous_variant	27/29	5		ENSP00000414125
DOCK5	ENST00000467709.6	c.*1343C>T		3_prime_UTR_variant, NMD_transcript_variant	18/36	5		ENSP00000428479

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70209 AN: 151892 Hom.: 16454 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.486

GnomAD3 exomes AF: 0.474 AC: 117252 AN: 247288 Hom.: 28397 AF XY: 0.479 AC XY: 64113 AN XY: 133770

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.395

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.483 AC: 703375 AN: 1457654 Hom.: 171248 Cov.: 44 AF XY: 0.483 AC XY: 350452 AN XY: 724936

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.487

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.462 AC: 70246 AN: 152010 Hom.: 16465 Cov.: 32 AF XY: 0.468 AC XY: 34791 AN XY: 74308

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.489

Alfa AF: 0.486 Hom.: 23182

Bravo AF: 0.447

Asia WGS AF: 0.454 AC: 1575 AN: 3478

EpiCase AF: 0.506

EpiControl AF: 0.499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.5
DANN	Benign	0.54

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: rs2271108; hg19: chr8-25230168; COSMIC: COSV52397056;