1-62531167-C-G

Variant names:

• chr1-62531167-C-G
• rs1168013
• NM_001367561.1:c.3612-1721G>C

Variant summary

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

The NM_001367561.1(DOCK7):​c.3612-1721G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,050 control chromosomes in the GnomAD database, including 27,536 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 0.58 (27536 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 46 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.3612-1721G>C		intron_variant	Intron 29 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.3612-1721G>C		intron_variant	Intron 29 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88651 AN: 151932 Hom.: 27531 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.583 AC: 88685 AN: 152050 Hom.: 27536 Cov.: 31 AF XY: 0.586 AC XY: 43558 AN XY: 74304

African (AFR) AF: 0.357 AC: 14798 AN: 41464

American (AMR) AF: 0.611 AC: 9343 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2640 AN: 3464

East Asian (EAS) AF: 0.757 AC: 3910 AN: 5164

South Asian (SAS) AF: 0.547 AC: 2634 AN: 4812

European-Finnish (FIN) AF: 0.750 AC: 7933 AN: 10576

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45329 AN: 67974

Other (OTH) AF: 0.639 AC: 1345 AN: 2106

Alfa AF: 0.506 Hom.: 1611

Bravo AF: 0.565

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.35
PhyloP100		-1.0
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: rs1168013; hg19: chr1-62996838;