Variant chr1-62494430-A-G 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.5062T>C(p.Leu1688=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,611,696 control chromosomes in the GnomAD database, including 100,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1688L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.35 ( 9341 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91072 hom. )

Consequence

DOCK7
NM_001367561.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0270

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=-0.77).

BP6

Variant 1-62494430-A-G is Benign according to our data. Variant chr1-62494430-A-G is described in ClinVar as [Benign]. Clinvar id is 585797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1 linkuse as main transcript	c.5062T>C	p.Leu1688=	synonymous_variant	40/50	ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2 linkuse as main transcript	c.5062T>C	p.Leu1688=	synonymous_variant	40/50	5	NM_001367561.1		Q96N67-1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52728

AN:

151932

Hom.:

9332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.343

AC:

86169

AN:

250866

Hom.:

15615

AF XY:

0.346

AC XY:

46840

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.391

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.460

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.349

AC:

509403

AN:

1459646

Hom.:

91072

Cov.:

AF XY:

0.351

AC XY:

254964

AN XY:

725840

show subpopulations

Gnomad4 AFR exome

AF:

0.394

Gnomad4 AMR exome

AF:

0.385

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.458

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.347

AC:

52768

AN:

152050

Hom.:

9341

Cov.:

AF XY:

0.346

AC XY:

25689

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.438

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.345

Hom.:

4534

Bravo

AF:

0.352

Asia WGS

AF:

0.377

AC:

1313

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	- -

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 58% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 54. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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