rs10238664

Variant names:

• chr7-111832984-G-A
• rs10238664
• NM_001363540.2:c.2835+1604C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-111832984-G-A
• chr7-111832984-G-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.2835+1604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,094 control chromosomes in the GnomAD database, including 15,167 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 (15167 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2835+1604C>T		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+1604C>T		intron_variant	Intron 26 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.2835+1604C>T		intron_variant	Intron 26 of 51	1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.1188+1604C>T		intron_variant	Intron 10 of 35	1		ENSP00000412834.1
DOCK4	ENST00000445943.5	c.2904+1604C>T		intron_variant	Intron 26 of 52	5		ENSP00000397412.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56152 AN: 151976 Hom.: 15132 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.370 AC: 56246 AN: 152094 Hom.: 15167 Cov.: 32 AF XY: 0.365 AC XY: 27137 AN XY: 74366

African (AFR) AF: 0.770 AC: 31905 AN: 41460

American (AMR) AF: 0.239 AC: 3651 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1871 AN: 5170

South Asian (SAS) AF: 0.156 AC: 755 AN: 4830

European-Finnish (FIN) AF: 0.256 AC: 2704 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13557 AN: 67980

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.244 Hom.: 25085

Bravo AF: 0.391

Asia WGS AF: 0.286 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.34
PhyloP100		-0.74
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: rs10238664; hg19: chr7-111473040;