Genetic Variant DOCK7:p.Gln150His (chr1-62648484-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367561.1(DOCK7):c.450A>C(p.Gln150His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q150Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

DOCK7
NM_001367561.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23648602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1 link	c.450A>C	p.Gln150His	missense_variant	Exon 5 of 50	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2 link	c.450A>C	p.Gln150His	missense_variant	Exon 5 of 50	5	NM_001367561.1	ENSP00000489124.1		Q96N67-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181218

AF XY:

0.0000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000131

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1376126

Hom.:

Cov.:

AF XY:

0.00000441

AC XY:

AN XY:

681024

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30530

American (AMR)

AF:

0.00

AC:

AN:

38168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24590

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

72598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4242

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1064762

Other (OTH)

AF:

0.00

AC:

AN:

56282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000167

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;.;.;.;.;T;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

T;T;D;D;D;T;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.24

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;L;L;L;L;L;L

PhyloP100

1.5

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.8

N;.;N;.;.;.;D

REVEL

Benign

0.26

Sift

Benign

0.42

T;.;T;.;.;.;T

Sift4G

Benign

0.34

T;T;T;T;T;T;T

Polyphen

1.0, 0.045, 1.0

.;D;D;B;D;.;.

Vest4

0.54

MutPred

0.19

Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);

MVP

0.76

MPC

0.36

ClinPred

0.33

GERP RS

2.0

Varity_R

0.23

gMVP

0.51

Mutation Taster

=65/35

polymorphism

(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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1-62648484-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over