Variant 7-111808875-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001363540.2(DOCK4):c.3112G>A(p.Gly1038Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DOCK4
NM_001363540.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.38

Variant links:

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]

DOCK4 links:

DOCK4-AS1 (HGNC:):

DOCK4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2 linkuse as main transcript	c.3112G>A	p.Gly1038Ser	missense_variant	30/53	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6 linkuse as main transcript	c.3112G>A	p.Gly1038Ser	missense_variant	30/53	5	NM_001363540.2	ENSP00000410746.1		Q8N1I0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726454

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DOCK4-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 12, 2023

The DOCK4 c.3112G>A variant is predicted to result in the amino acid substitution p.Gly1038Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

.;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.1

D;D;.

REVEL

Uncertain

0.36

Sift

Benign

0.031

D;D;.

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.78

.;P;.

Vest4

0.82

MutPred

0.69

Loss of catalytic residue at G1038 (P = 0.0646);Loss of catalytic residue at G1038 (P = 0.0646);.;

MVP

0.72

MPC

0.57

ClinPred

0.99

GERP RS

5.4

Varity_R

0.68

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over