rs11207997

Variant names:

• chr1-62596235-C-T
• rs11207997
• NM_001367561.1:c.1683-9611G>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.1683-9611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,876 control chromosomes in the GnomAD database, including 12,457 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 0.39 (12457 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 24 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1683-9611G>A		intron_variant	Intron 14 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1683-9611G>A		intron_variant	Intron 14 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59226 AN: 151758 Hom.: 12432 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.390 AC: 59301 AN: 151876 Hom.: 12457 Cov.: 31 AF XY: 0.389 AC XY: 28843 AN XY: 74220

African (AFR) AF: 0.552 AC: 22883 AN: 41418

American (AMR) AF: 0.378 AC: 5760 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5174

South Asian (SAS) AF: 0.452 AC: 2172 AN: 4808

European-Finnish (FIN) AF: 0.249 AC: 2622 AN: 10528

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22610 AN: 67924

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.356 Hom.: 13620

Bravo AF: 0.405

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.62
PhyloP100		-0.17
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: rs11207997; hg19: chr1-63061906;