chr7-111846970-G-A

Variant names:

• chr7-111846970-G-A
• rs10275038
• NM_001363540.2:c.2601+29C>T

Variant summary

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

The NM_001363540.2(DOCK4):​c.2601+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,608,382 control chromosomes in the GnomAD database, including 58,457 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 0.38 (16028 hom., cov: 32)
  • Exomes 𝑓: 0.22 (42429 hom.)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 11 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2601+29C>T		intron_variant	Intron 24 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.2601+29C>T		intron_variant	Intron 24 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.2601+29C>T		intron_variant	Intron 24 of 51	1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.954+29C>T		intron_variant	Intron 8 of 35	1		ENSP00000412834.1
DOCK4	ENST00000445943.5	c.2562+29C>T		intron_variant	Intron 23 of 52	5		ENSP00000397412.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56938 AN: 151984 Hom.: 15977 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.248 AC: 61348 AN: 247768 AF XY: 0.238

Gnomad AFR exome AF: 0.815

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.221 AC: 322080 AN: 1456280 Hom.: 42429 Cov.: 30 AF XY: 0.219 AC XY: 158478 AN XY: 724296

African (AFR) AF: 0.825 AC: 27497 AN: 33348

American (AMR) AF: 0.201 AC: 8977 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6605 AN: 25992

East Asian (EAS) AF: 0.215 AC: 8520 AN: 39610

South Asian (SAS) AF: 0.198 AC: 16979 AN: 85584

European-Finnish (FIN) AF: 0.219 AC: 11650 AN: 53126

Middle Eastern (MID) AF: 0.255 AC: 1457 AN: 5720

European-Non Finnish (NFE) AF: 0.203 AC: 225037 AN: 1108236

Other (OTH) AF: 0.256 AC: 15358 AN: 60096

GnomAD4 genome AF: 0.375 AC: 57051 AN: 152102 Hom.: 16028 Cov.: 32 AF XY: 0.368 AC XY: 27362 AN XY: 74352

African (AFR) AF: 0.797 AC: 33082 AN: 41486

American (AMR) AF: 0.245 AC: 3751 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3468

East Asian (EAS) AF: 0.236 AC: 1218 AN: 5166

South Asian (SAS) AF: 0.182 AC: 881 AN: 4828

European-Finnish (FIN) AF: 0.220 AC: 2332 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13901 AN: 67978

Other (OTH) AF: 0.345 AC: 727 AN: 2108

Alfa AF: 0.258 Hom.: 28196

Bravo AF: 0.399

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.60
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10275038; hg19: chr7-111487026; COSMIC: COSV70237538;