chr1-62648297-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367561.1(DOCK7):c.541A>G(p.Met181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,611,734 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M181L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.039 ( 346 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 562 hom. )

Consequence

DOCK7
NM_001367561.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.29

Publications

7 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

DOCK7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019033551).

BP6

Variant 1-62648297-T-C is Benign according to our data. Variant chr1-62648297-T-C is described in ClinVar as Benign. ClinVar VariationId is 447277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 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	UniProt
DOCK7	NM_001367561.1	MANE Select	c.541A>G	p.Met181Val	missense	Exon 6 of 50	NP_001354490.1	Q96N67-1
DOCK7	NM_001330614.2		c.541A>G	p.Met181Val	missense	Exon 6 of 50	NP_001317543.1	Q96N67-6
DOCK7	NM_001271999.2		c.541A>G	p.Met181Val	missense	Exon 6 of 49	NP_001258928.1	Q96N67-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.541A>G	p.Met181Val	missense	Exon 6 of 50	ENSP00000489124.1	Q96N67-1
DOCK7	ENST00000454575.6	TSL:1	c.541A>G	p.Met181Val	missense	Exon 6 of 49	ENSP00000413583.2	Q96N67-2
DOCK7	ENST00000912940.1		c.541A>G	p.Met181Val	missense	Exon 6 of 49	ENSP00000582999.1

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5861

AN:

152076

Hom.:

347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0297

GnomAD2 exomes

AF:

0.0183

AC:

4566

AN:

249086

AF XY:

0.0154

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00473

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000826

Gnomad OTH exome

AF:

0.00827

GnomAD4 exome

AF:

0.00741

AC:

10814

AN:

1459540

Hom.:

562

Cov.:

AF XY:

0.00695

AC XY:

5047

AN XY:

726046

show subpopulations

African (AFR)

AF:

0.117

AC:

3924

AN:

33440

American (AMR)

AF:

0.00569

AC:

254

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00315

AC:

AN:

26050

East Asian (EAS)

AF:

0.121

AC:

4802

AN:

39610

South Asian (SAS)

AF:

0.00519

AC:

445

AN:

85808

European-Finnish (FIN)

AF:

0.0000751

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000456

AC:

506

AN:

1110674

Other (OTH)

AF:

0.0129

AC:

778

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

501

1001

1502

2002

2503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<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:

0.0385

AC:

5862

AN:

152194

Hom.:

346

Cov.:

AF XY:

0.0384

AC XY:

2856

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.118

AC:

4885

AN:

41516

American (AMR)

AF:

0.0132

AC:

202

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3466

East Asian (EAS)

AF:

0.121

AC:

630

AN:

5188

South Asian (SAS)

AF:

0.00766

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

67980

Other (OTH)

AF:

0.0294

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

263

526

789

1052

1315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0189

Hom.:

247

Bravo

AF:

0.0438

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.110

AC:

484

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.0208

AC:

2525

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy, 23 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.084

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.1

PhyloP100

1.3

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.24

REVEL

Benign

0.14

Sift

Benign

0.71

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.095

MPC

0.39

ClinPred

0.00074

GERP RS

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.41

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over