1-62503731-G-A

Variant names:

• chr1-62503731-G-A
• rs1168029
• NM_001367561.1:c.4764+899C>T

Variant summary

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

The NM_001367561.1(DOCK7):​c.4764+899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,830 control chromosomes in the GnomAD database, including 26,786 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 0.57 (26786 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 29 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367561.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	NM_001367561.1	MANE Select	c.4764+899C>T		intron	N/A	NP_001354490.1
	DOCK7	NM_001330614.2		c.4737+899C>T		intron	N/A	NP_001317543.1
	DOCK7	NM_001271999.2		c.4737+899C>T		intron	N/A	NP_001258928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.4764+899C>T		intron	N/A	ENSP00000489124.1
	DOCK7	ENST00000454575.6	TSL:1	c.4737+899C>T		intron	N/A	ENSP00000413583.2
	DOCK7	ENST00000251157.10	TSL:5	c.4737+899C>T		intron	N/A	ENSP00000251157.6

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87239 AN: 151712 Hom.: 26788 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.575 AC: 87253 AN: 151830 Hom.: 26786 Cov.: 31 AF XY: 0.576 AC XY: 42753 AN XY: 74174

African (AFR) AF: 0.344 AC: 14231 AN: 41408

American (AMR) AF: 0.607 AC: 9273 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2628 AN: 3466

East Asian (EAS) AF: 0.757 AC: 3854 AN: 5092

South Asian (SAS) AF: 0.538 AC: 2588 AN: 4808

European-Finnish (FIN) AF: 0.728 AC: 7678 AN: 10542

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44926 AN: 67928

Other (OTH) AF: 0.630 AC: 1330 AN: 2110

Alfa AF: 0.655 Hom.: 71231

Bravo AF: 0.558

Asia WGS AF: 0.555 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.44
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: rs1168029; hg19: chr1-62969402;