Variant chr1-62633567-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001367561.1(DOCK7):c.1047C>T(p.Val349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,611,876 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V349V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

DOCK7
NM_001367561.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.859

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-62633567-G-A is Benign according to our data. Variant chr1-62633567-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-62633567-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.859 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00293 (446/152160) while in subpopulation NFE AF= 0.00537 (365/68012). AF 95% confidence interval is 0.00491. There are 1 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1 linkuse as main transcript	c.1047C>T	p.Val349=	synonymous_variant	10/50	ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2 linkuse as main transcript	c.1047C>T	p.Val349=	synonymous_variant	10/50	5	NM_001367561.1		Q96N67-1

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

446

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00269

AC:

671

AN:

249642

Hom.:

AF XY:

0.00271

AC XY:

365

AN XY:

134914

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.000732

Gnomad ASJ exome

AF:

0.00528

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000529

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00460

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00440

AC:

6416

AN:

1459716

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

3113

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.000742

Gnomad4 ASJ exome

AF:

0.00648

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000617

Gnomad4 FIN exome

AF:

0.00205

Gnomad4 NFE exome

AF:

0.00517

Gnomad4 OTH exome

AF:

0.00463

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152160

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000819

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00537

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00340

Hom.:

Bravo

AF:

0.00284

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00395

EpiControl

AF:

0.00357

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	DOCK7: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 05, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 22, 2021	- -

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	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.5

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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