rs10255299

Positions:

• chr7-111887504-G-A
• chr7-111887504-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):​c.1587+8108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,100 control chromosomes in the GnomAD database, including 1,063 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 0.11 (1063 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.1587+8108C>T		intron_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.1587+8108C>T		intron_variant		5	NM_001363540.2	ENSP00000410746	P3
DOCK4	ENST00000437633.6	c.1587+8108C>T		intron_variant		1		ENSP00000404179	A1
DOCK4	ENST00000445943.5	c.1550+8108C>T		intron_variant		5		ENSP00000397412
DOCK4	ENST00000476846.5	n.1843+8108C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16117 AN: 151982 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00695

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.106 AC: 16165 AN: 152100 Hom.: 1063 Cov.: 32 AF XY: 0.105 AC XY: 7822 AN XY: 74366

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00697

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0774

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0793 Hom.: 970

Bravo AF: 0.107

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
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: rs10255299; hg19: chr7-111527560;