chr8-25372652-C-T

Variant names:

• chr8-25372652-C-T
• rs2271108
• NM_024940.8:c.3618C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_024940.8(DOCK5):​c.3618C>T​(p.Asp1206Asp) 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
• Publications: 21 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 -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 rank	MANE	Protein	UniProt
DOCK5	NM_024940.8	c.3618C>T	p.Asp1206Asp	synonymous_variant	Exon 35 of 52	ENST00000276440.12	NP_079216.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK5	ENST00000276440.12	c.3618C>T	p.Asp1206Asp	synonymous_variant	Exon 35 of 52	1	NM_024940.8	ENSP00000276440.7
DOCK5	ENST00000444569.5	c.2931C>T	p.Asp977Asp	synonymous_variant	Exon 27 of 29	5		ENSP00000414125.1
DOCK5	ENST00000467709.6	n.*1343C>T		non_coding_transcript_exon_variant	Exon 18 of 36	5		ENSP00000428479.1
DOCK5	ENST00000467709.6	n.*1343C>T		3_prime_UTR_variant	Exon 18 of 36	5		ENSP00000428479.1

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

GnomAD2 exomes AF: 0.474 AC: 117252 AN: 247288 AF XY: 0.479

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 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

African (AFR) AF: 0.381 AC: 12672 AN: 33300

American (AMR) AF: 0.403 AC: 17752 AN: 44074

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 13381 AN: 26014

East Asian (EAS) AF: 0.380 AC: 15013 AN: 39492

South Asian (SAS) AF: 0.483 AC: 41206 AN: 85388

European-Finnish (FIN) AF: 0.580 AC: 30956 AN: 53336

Middle Eastern (MID) AF: 0.549 AC: 3156 AN: 5744

European-Non Finnish (NFE) AF: 0.487 AC: 540411 AN: 1110084

Other (OTH) AF: 0.479 AC: 28828 AN: 60222

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

African (AFR) AF: 0.386 AC: 16018 AN: 41450

American (AMR) AF: 0.457 AC: 6992 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1766 AN: 3466

East Asian (EAS) AF: 0.410 AC: 2116 AN: 5160

South Asian (SAS) AF: 0.480 AC: 2304 AN: 4802

European-Finnish (FIN) AF: 0.593 AC: 6268 AN: 10562

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33240 AN: 67954

Other (OTH) AF: 0.489 AC: 1032 AN: 2112

Alfa AF: 0.482 Hom.: 28081

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
PhyloP100		0.49
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: rs2271108; hg19: chr8-25230168; COSMIC: COSV52397056;