rs10493326

Variant names:

• chr1-62487702-G-A
• rs10493326
• NM_001367561.1:c.5494-290C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367561.1(DOCK7):​c.5494-290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 293,872 control chromosomes in the GnomAD database, including 7,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3462 hom., cov: 32)
  • Exomes 𝑓: 0.23 (4146 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.74
• Publications: 15 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 1-62487702-G-A is Benign according to our data. Variant chr1-62487702-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.5494-290C>T		intron_variant	Intron 42 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.5494-290C>T		intron_variant	Intron 42 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30068 AN: 151912 Hom.: 3456 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.231 AC: 32765 AN: 141840 Hom.: 4146 Cov.: 0 AF XY: 0.229 AC XY: 16756 AN XY: 73148

African (AFR) AF: 0.0691 AC: 364 AN: 5266

American (AMR) AF: 0.210 AC: 1302 AN: 6202

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 1151 AN: 5140

East Asian (EAS) AF: 0.152 AC: 1789 AN: 11742

South Asian (SAS) AF: 0.190 AC: 1871 AN: 9868

European-Finnish (FIN) AF: 0.268 AC: 1693 AN: 6314

Middle Eastern (MID) AF: 0.184 AC: 125 AN: 678

European-Non Finnish (NFE) AF: 0.255 AC: 22360 AN: 87568

Other (OTH) AF: 0.233 AC: 2110 AN: 9062

GnomAD4 genome AF: 0.198 AC: 30087 AN: 152032 Hom.: 3462 Cov.: 32 AF XY: 0.199 AC XY: 14794 AN XY: 74300

African (AFR) AF: 0.0722 AC: 2998 AN: 41520

American (AMR) AF: 0.230 AC: 3510 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3468

East Asian (EAS) AF: 0.139 AC: 718 AN: 5166

South Asian (SAS) AF: 0.201 AC: 970 AN: 4816

European-Finnish (FIN) AF: 0.285 AC: 3011 AN: 10562

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17415 AN: 67906

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.236 Hom.: 12654

Bravo AF: 0.186

Asia WGS AF: 0.168 AC: 583 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.079
DANN	Benign	0.45
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10493326; hg19: chr1-62953373;