rs10487338

Positions:

• chr7-112079789-A-C
• chr7-112079789-A-T

Variant summary

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

The NM_001363540.2(DOCK4):​c.38-75658T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,254 control chromosomes in the GnomAD database, including 880 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 0.079 (880 hom., cov: 33)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.38-75658T>G		intron_variant		ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.38-75658T>G		intron_variant		5	NM_001363540.2	P3
DOCK4	ENST00000437633.6	c.38-75658T>G		intron_variant		1		A1
DOCK4	ENST00000476846.5	n.294-75658T>G		intron_variant, non_coding_transcript_variant		5
DOCK4	ENST00000661654.1	n.307-75658T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11990 AN: 152136 Hom.: 882 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0787 AC: 11987 AN: 152254 Hom.: 880 Cov.: 33 AF XY: 0.0819 AC XY: 6101 AN XY: 74452

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0508

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0334

Gnomad4 NFE AF: 0.0441

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0564 Hom.: 50

Bravo AF: 0.0878

Asia WGS AF: 0.245 AC: 853 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.45

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: rs10487338; hg19: chr7-111719844;