7-111829516-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2835+5072G>A		intron_variant	Intron 26 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.2835+5072G>A		intron_variant	Intron 26 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.2835+5072G>A		intron_variant	Intron 26 of 51	1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.1188+5072G>A		intron_variant	Intron 10 of 35	1		ENSP00000412834.1
DOCK4	ENST00000445943.5	c.2904+5072G>A		intron_variant	Intron 26 of 52	5		ENSP00000397412.1

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

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.335

Alfa AF: 0.288 Hom.: 3004

Bravo AF: 0.393

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.46

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: rs6966622; hg19: chr7-111469572;