dbSNP rs1168029: DOCK7:c.4764+899C>T (chr1-62503731-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001367561.1(DOCK7):c.4764+899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,830 control chromosomes in the GnomAD database, including 26,786 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 26786 hom., cov: 31)

Consequence

DOCK7
NM_001367561.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

29 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 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	Effect	Exon Rank	Protein	UniProt
DOCK7	NM_001367561.1	MANE Select	c.4764+899C>T	intron	N/A	NP_001354490.1	Q96N67-1
DOCK7	NM_001330614.2		c.4737+899C>T	intron	N/A	NP_001317543.1	Q96N67-6
DOCK7	NM_001271999.2		c.4737+899C>T	intron	N/A	NP_001258928.1	Q96N67-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.4764+899C>T	intron	N/A	ENSP00000489124.1	Q96N67-1
DOCK7	ENST00000454575.6	TSL:1	c.4737+899C>T	intron	N/A	ENSP00000413583.2	Q96N67-2
DOCK7	ENST00000912940.1		c.4764+899C>T	intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87239

AN:

151712

Hom.:

26788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.758

Gnomad EAS

AF:

0.757

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.728

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.575

AC:

87253

AN:

151830

Hom.:

26786

Cov.:

AF XY:

0.576

AC XY:

42753

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.344

AC:

14231

AN:

41408

American (AMR)

AF:

0.607

AC:

9273

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.758

AC:

2628

AN:

3466

East Asian (EAS)

AF:

0.757

AC:

3854

AN:

5092

South Asian (SAS)

AF:

0.538

AC:

2588

AN:

4808

European-Finnish (FIN)

AF:

0.728

AC:

7678

AN:

10542

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.661

AC:

44926

AN:

67928

Other (OTH)

AF:

0.630

AC:

1330

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1724

3449

5173

6898

8622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.655

Hom.:

71231

Bravo

AF:

0.558

Asia WGS

AF:

0.555

AC:

1928

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.3

(source)

DANN

Benign

0.44

PhyloP100

-1.0

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over