chr1-62494430-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001367561.1(DOCK7):c.5062T>C(p.Leu1688Leu) 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. 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

Publications

32 publications found

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 23
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

DOCK7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-62494430-A-G is Benign according to our data. Variant chr1-62494430-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367561.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DOCK7	NM_001367561.1	MANE Select	c.5062T>C	p.Leu1688Leu	synonymous	Exon 40 of 50	NP_001354490.1
DOCK7	NM_001330614.2		c.5035T>C	p.Leu1679Leu	synonymous	Exon 40 of 50	NP_001317543.1
DOCK7	NM_001271999.2		c.5035T>C	p.Leu1679Leu	synonymous	Exon 40 of 49	NP_001258928.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.5062T>C	p.Leu1688Leu	synonymous	Exon 40 of 50	ENSP00000489124.1
DOCK7	ENST00000454575.6	TSL:1	c.5035T>C	p.Leu1679Leu	synonymous	Exon 40 of 49	ENSP00000413583.2
DOCK7	ENST00000251157.10	TSL:5	c.5035T>C	p.Leu1679Leu	synonymous	Exon 40 of 50	ENSP00000251157.6

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

GnomAD2 exomes

AF:

0.343

AC:

86169

AN:

250866

AF XY:

0.346

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 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

African (AFR)

AF:

0.394

AC:

13163

AN:

33446

American (AMR)

AF:

0.385

AC:

17190

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5985

AN:

26100

East Asian (EAS)

AF:

0.168

AC:

6654

AN:

39644

South Asian (SAS)

AF:

0.458

AC:

39419

AN:

86042

European-Finnish (FIN)

AF:

0.284

AC:

15148

AN:

53364

Middle Eastern (MID)

AF:

0.302

AC:

1740

AN:

5758

European-Non Finnish (NFE)

AF:

0.351

AC:

389753

AN:

1110338

Other (OTH)

AF:

0.338

AC:

20351

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17350

34700

52050

69400

86750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12618

25236

37854

50472

63090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.347

AC:

52768

AN:

152050

Hom.:

9341

Cov.:

AF XY:

0.346

AC XY:

25689

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.398

AC:

16483

AN:

41464

American (AMR)

AF:

0.345

AC:

5271

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3470

East Asian (EAS)

AF:

0.186

AC:

959

AN:

5166

South Asian (SAS)

AF:

0.438

AC:

2104

AN:

4808

European-Finnish (FIN)

AF:

0.274

AC:

2895

AN:

10576

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23117

AN:

67974

Other (OTH)

AF:

0.312

AC:

660

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1747

3493

5240

6986

8733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.353

Hom.:

5571

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

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Developmental and epileptic encephalopathy, 23

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

(source)

DANN

Benign

0.56

PhyloP100

-0.027

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over