Variant rs17123688 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367561.1(DOCK7):c.4283-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,610,796 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 254 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 433 hom. )

Consequence

DOCK7
NM_001367561.1 splice_region, intron

Scores

Splicing: ADA: 0.009862

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.321

Variant links:

Genes affected

DOCK7 (HGNC:19190): (dedicator of cytokinesis 7) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

DOCK7 links:

DOCK7 (HGNC:):

DOCK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-62510677-T-C is Benign according to our data. Variant chr1-62510677-T-C is described in ClinVar as [Benign]. Clinvar id is 475145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK7	NM_001367561.1 linkuse as main transcript	c.4283-4A>G		splice_region_variant, intron_variant		ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2 linkuse as main transcript	c.4283-4A>G		splice_region_variant, intron_variant		5	NM_001367561.1	ENSP00000489124.1		Q96N67-1

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

5569

AN:

152146

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.0539

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.0277

GnomAD3 exomes

AF:

0.0186

AC:

4650

AN:

249428

Hom.:

140

AF XY:

0.0167

AC XY:

2245

AN XY:

134828

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.0242

Gnomad ASJ exome

AF:

0.00798

Gnomad EAS exome

AF:

0.0486

Gnomad SAS exome

AF:

0.0296

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00854

AC:

12455

AN:

1458532

Hom.:

433

Cov.:

AF XY:

0.00881

AC XY:

6391

AN XY:

725602

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0257

Gnomad4 ASJ exome

AF:

0.00798

Gnomad4 EAS exome

AF:

0.0627

Gnomad4 SAS exome

AF:

0.0292

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0367

AC:

5591

AN:

152264

Hom.:

254

Cov.:

AF XY:

0.0372

AC XY:

2766

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0354

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.0537

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0407

Asia WGS

AF:

0.0650

AC:

224

AN:

3474

EpiCase

AF:

0.00137

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 15, 2017	- -

Developmental and epileptic encephalopathy, 23

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.4

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0099

dbscSNV1_RF

Benign

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over