rs17158930

Variant names:

• chr7-111871082-A-G
• rs17158930
• NM_001363540.2:c.2027+908T>C

Variant summary

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

The NM_001363540.2(DOCK4):​c.2027+908T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,156 control chromosomes in the GnomAD database, including 5,304 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 0.24 (5304 hom., cov: 33)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	NM_001363540.2	MANE Select	c.2027+908T>C		intron	N/A	NP_001350469.1
	DOCK4	NM_014705.4		c.2027+908T>C		intron	N/A	NP_055520.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.2027+908T>C		intron	N/A	ENSP00000410746.1
	DOCK4	ENST00000437633.6	TSL:1	c.2027+908T>C		intron	N/A	ENSP00000404179.1
	DOCK4	ENST00000423057.6	TSL:1	c.380+908T>C		intron	N/A	ENSP00000412834.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36953 AN: 152040 Hom.: 5297 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.243 AC: 36991 AN: 152156 Hom.: 5304 Cov.: 33 AF XY: 0.242 AC XY: 17970 AN XY: 74386

African (AFR) AF: 0.396 AC: 16435 AN: 41474

American (AMR) AF: 0.218 AC: 3329 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3472

East Asian (EAS) AF: 0.148 AC: 765 AN: 5178

South Asian (SAS) AF: 0.137 AC: 661 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2127 AN: 10592

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12385 AN: 67998

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.195 Hom.: 13852

Bravo AF: 0.254

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.72
PhyloP100		0.17
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: rs17158930; hg19: chr7-111511138; COSMIC: COSV70244191;