7-111829516-C-T

Variant names:

• chr7-111829516-C-T
• rs6966622
• NM_001363540.2:c.2835+5072G>A

Variant summary

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

The NM_001363540.2(DOCK4):​c.2835+5072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,056 control chromosomes in the GnomAD database, including 15,691 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 0.37 (15691 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 4 publications found

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363540.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	NM_001363540.2	MANE Select	c.2835+5072G>A		intron	N/A	NP_001350469.1	Q8N1I0-3
	DOCK4	NM_014705.4		c.2835+5072G>A		intron	N/A	NP_055520.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.2835+5072G>A		intron	N/A	ENSP00000410746.1	Q8N1I0-3
	DOCK4	ENST00000437633.6	TSL:1	c.2835+5072G>A		intron	N/A	ENSP00000404179.1	Q8N1I0-1
	DOCK4	ENST00000423057.6	TSL:1	c.1188+5072G>A		intron	N/A	ENSP00000412834.1	H0Y7H7

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55869 AN: 151938 Hom.: 15650 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.368 AC: 55969 AN: 152056 Hom.: 15691 Cov.: 32 AF XY: 0.363 AC XY: 27014 AN XY: 74328

African (AFR) AF: 0.792 AC: 32844 AN: 41452

American (AMR) AF: 0.239 AC: 3642 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1882 AN: 5168

South Asian (SAS) AF: 0.162 AC: 780 AN: 4822

European-Finnish (FIN) AF: 0.234 AC: 2477 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12546 AN: 67994

Other (OTH) AF: 0.335 AC: 708 AN: 2114

Alfa AF: 0.285 Hom.: 5811

Bravo AF: 0.393

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-1.1
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: rs6966622; hg19: chr7-111469572;