1-62652525-A-C

Variant names:

• chr1-62652525-A-C
• rs10889353
• NM_001367561.1:c.389+1200T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367561.1(DOCK7):​c.389+1200T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,716 control chromosomes in the GnomAD database, including 8,616 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 0.33 (8616 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 109 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.389+1200T>G		intron_variant	Intron 4 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.389+1200T>G		intron_variant	Intron 4 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50639 AN: 151598 Hom.: 8605 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.334 AC: 50677 AN: 151716 Hom.: 8616 Cov.: 31 AF XY: 0.332 AC XY: 24600 AN XY: 74094

African (AFR) AF: 0.377 AC: 15589 AN: 41338

American (AMR) AF: 0.336 AC: 5112 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3466

East Asian (EAS) AF: 0.189 AC: 974 AN: 5156

South Asian (SAS) AF: 0.419 AC: 2011 AN: 4800

European-Finnish (FIN) AF: 0.249 AC: 2618 AN: 10512

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22501 AN: 67908

Other (OTH) AF: 0.298 AC: 626 AN: 2102

Alfa AF: 0.327 Hom.: 29919

Bravo AF: 0.341

Asia WGS AF: 0.367 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		1.4
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: rs10889353; hg19: chr1-63118196;