rs10889335

Variant names:

• chr1-62494430-A-G
• rs10889335
• NM_001367561.1:c.5062T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. In-silico tool predicts a benign outcome for this variant. 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0270

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-62494430-A-G is Benign according to our data. Variant chr1-62494430-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.5062T>C	p.Leu1688Leu	synonymous_variant	Exon 40 of 50	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.5062T>C	p.Leu1688Leu	synonymous_variant	Exon 40 of 50	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52728 AN: 151932 Hom.: 9332 Cov.: 32

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

GnomAD3 exomes AF: 0.343 AC: 86169 AN: 250866 Hom.: 15615 AF XY: 0.346 AC XY: 46840 AN XY: 135550

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 SAS exome AF: 0.460

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.: 36 AF XY: 0.351 AC XY: 254964 AN XY: 725840

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.347 AC: 52768 AN: 152050 Hom.: 9341 Cov.: 32 AF XY: 0.346 AC XY: 25689 AN XY: 74302

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.312

Alfa AF: 0.345 Hom.: 4534

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

Submissions by phenotype

not provided Benign:3

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

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 23 Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs10889335; hg19: chr1-62960101; COSMIC: COSV52012440; COSMIC: COSV52012440;