1-62485187-C-T

Variant names:

• chr1-62485187-C-T
• rs10889332
• NM_001367561.1:c.5508+2211G>A

Variant summary

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

The NM_001367561.1(DOCK7):​c.5508+2211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 984,404 control chromosomes in the GnomAD database, including 65,663 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 0.38 (11968 hom., cov: 32)
  • Exomes 𝑓: 0.36 (53695 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 42 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	NM_001367561.1	MANE Select	c.5508+2211G>A		intron	N/A	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.5481+2211G>A		intron	N/A	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.5466+3747G>A		intron	N/A	NP_001258928.1	Q96N67-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.5508+2211G>A		intron	N/A	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.5466+3747G>A		intron	N/A	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.5493+3747G>A		intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58304 AN: 151648 Hom.: 11944 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.358 AC: 297755 AN: 832640 Hom.: 53695 Cov.: 30 AF XY: 0.358 AC XY: 137660 AN XY: 384526

African (AFR) AF: 0.548 AC: 8647 AN: 15776

American (AMR) AF: 0.377 AC: 371 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 1168 AN: 5150

East Asian (EAS) AF: 0.252 AC: 914 AN: 3628

South Asian (SAS) AF: 0.458 AC: 7527 AN: 16450

European-Finnish (FIN) AF: 0.268 AC: 74 AN: 276

Middle Eastern (MID) AF: 0.325 AC: 526 AN: 1616

European-Non Finnish (NFE) AF: 0.353 AC: 268786 AN: 761476

Other (OTH) AF: 0.357 AC: 9742 AN: 27284

GnomAD4 genome AF: 0.385 AC: 58378 AN: 151764 Hom.: 11968 Cov.: 32 AF XY: 0.384 AC XY: 28443 AN XY: 74138

African (AFR) AF: 0.530 AC: 21903 AN: 41328

American (AMR) AF: 0.377 AC: 5745 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1270 AN: 5172

South Asian (SAS) AF: 0.449 AC: 2162 AN: 4820

European-Finnish (FIN) AF: 0.252 AC: 2638 AN: 10480

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22662 AN: 67938

Other (OTH) AF: 0.341 AC: 718 AN: 2106

Alfa AF: 0.352 Hom.: 6325

Bravo AF: 0.397

Asia WGS AF: 0.434 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.57
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: rs10889332; hg19: chr1-62950858;