Variant rs3850634 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.1800+1580A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 679,296 control chromosomes in the GnomAD database, including 37,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8662 hom., cov: 31)

Exomes 𝑓: 0.32 ( 28987 hom. )

Consequence

DOCK7
NM_001367561.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.532

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:

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=-0.52).

BP6

Variant 1-62584927-T-G is Benign according to our data. Variant chr1-62584927-T-G is described in ClinVar as [Benign]. Clinvar id is 1227339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 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.1800+1580A>C		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.1800+1580A>C		intron_variant		5	NM_001367561.1	ENSP00000489124		Q96N67-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50754

AN:

151754

Hom.:

8651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.328

AC:

39898

AN:

121514

Hom.:

6937

AF XY:

0.335

AC XY:

22053

AN XY:

65840

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.322

AC:

170043

AN:

527424

Hom.:

28987

Cov.:

AF XY:

0.329

AC XY:

93781

AN XY:

285256

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.334

AC:

50792

AN:

151872

Hom.:

8662

Cov.:

AF XY:

0.332

AC XY:

24683

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.378

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.329

Hom.:

2980

Bravo

AF:

0.342

Asia WGS

AF:

0.367

AC:

1277

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 51. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

DANN

Benign

0.74

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

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