rs11207993

Variant names:

• chr1-62578793-C-T
• rs11207993
• NM_001367561.1:c.2010+35G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367561.1(DOCK7):​c.2010+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,475,086 control chromosomes in the GnomAD database, including 20,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1433 hom., cov: 28)
  • Exomes 𝑓: 0.17 (19264 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.56
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-62578793-C-T is Benign according to our data. Variant chr1-62578793-C-T is described in ClinVar as Benign. ClinVar VariationId is 1296220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.2010+35G>A		intron_variant	Intron 17 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.2010+35G>A		intron_variant	Intron 17 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 18968 AN: 148726 Hom.: 1432 Cov.: 28

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000787

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.140 AC: 27538 AN: 196066 AF XY: 0.141

Gnomad AFR exome AF: 0.0515

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.00121

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.166 AC: 219962 AN: 1326312 Hom.: 19264 Cov.: 23 AF XY: 0.164 AC XY: 108364 AN XY: 660346

African (AFR) AF: 0.0483 AC: 1313 AN: 27188

American (AMR) AF: 0.182 AC: 5042 AN: 27650

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2677 AN: 22330

East Asian (EAS) AF: 0.000614 AC: 20 AN: 32560

South Asian (SAS) AF: 0.118 AC: 8447 AN: 71888

European-Finnish (FIN) AF: 0.158 AC: 7800 AN: 49300

Middle Eastern (MID) AF: 0.115 AC: 478 AN: 4172

European-Non Finnish (NFE) AF: 0.180 AC: 186390 AN: 1037398

Other (OTH) AF: 0.145 AC: 7795 AN: 53826

GnomAD4 genome AF: 0.128 AC: 18969 AN: 148774 Hom.: 1433 Cov.: 28 AF XY: 0.127 AC XY: 9184 AN XY: 72276

African (AFR) AF: 0.0554 AC: 2250 AN: 40584

American (AMR) AF: 0.156 AC: 2326 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 400 AN: 3454

East Asian (EAS) AF: 0.000986 AC: 5 AN: 5070

South Asian (SAS) AF: 0.108 AC: 508 AN: 4718

European-Finnish (FIN) AF: 0.148 AC: 1368 AN: 9254

Middle Eastern (MID) AF: 0.0957 AC: 27 AN: 282

European-Non Finnish (NFE) AF: 0.173 AC: 11680 AN: 67526

Other (OTH) AF: 0.111 AC: 228 AN: 2060

Alfa AF: 0.159 Hom.: 3280

Bravo AF: 0.126

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.093
DANN	Benign	0.30
PhyloP100		-1.6
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: rs11207993; hg19: chr1-63044464;