1-62633352-T-C

Variant names:

• chr1-62633352-T-C
• rs10889352
• NM_001367561.1:c.1116+146A>G

Variant summary

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

The ENST00000635253.2(DOCK7):​c.1116+146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 586,968 control chromosomes in the GnomAD database, including 32,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8739 hom., cov: 31)
  • Exomes 𝑓: 0.32 (23788 hom.)
• Consequence: DOCK7 ENST00000635253.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.828
• Publications: 15 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=-0.87).
• BP6: Variant 1-62633352-T-C is Benign according to our data. Variant chr1-62633352-T-C is described in ClinVar as Benign. ClinVar VariationId is 1296214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635253.2. 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.1116+146A>G		intron	N/A	NP_001354490.1
	DOCK7	NM_001330614.2		c.1116+146A>G		intron	N/A	NP_001317543.1
	DOCK7	NM_001271999.2		c.1116+146A>G		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.1116+146A>G		intron	N/A	ENSP00000489124.1
	DOCK7	ENST00000454575.6	TSL:1	c.1116+146A>G		intron	N/A	ENSP00000413583.2
	DOCK7	ENST00000251157.10	TSL:5	c.1116+146A>G		intron	N/A	ENSP00000251157.6

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50960 AN: 151770 Hom.: 8728 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.321 AC: 139659 AN: 435078 Hom.: 23788 AF XY: 0.325 AC XY: 75243 AN XY: 231800

African (AFR) AF: 0.382 AC: 4335 AN: 11334

American (AMR) AF: 0.371 AC: 7146 AN: 19246

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 2786 AN: 12326

East Asian (EAS) AF: 0.160 AC: 4738 AN: 29572

South Asian (SAS) AF: 0.437 AC: 13299 AN: 30436

European-Finnish (FIN) AF: 0.261 AC: 9002 AN: 34492

Middle Eastern (MID) AF: 0.273 AC: 862 AN: 3152

European-Non Finnish (NFE) AF: 0.332 AC: 89648 AN: 270212

Other (OTH) AF: 0.323 AC: 7843 AN: 24308

GnomAD4 genome AF: 0.336 AC: 50999 AN: 151890 Hom.: 8739 Cov.: 31 AF XY: 0.334 AC XY: 24784 AN XY: 74256

African (AFR) AF: 0.382 AC: 15843 AN: 41428

American (AMR) AF: 0.336 AC: 5134 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3464

East Asian (EAS) AF: 0.190 AC: 981 AN: 5162

South Asian (SAS) AF: 0.420 AC: 2022 AN: 4810

European-Finnish (FIN) AF: 0.250 AC: 2636 AN: 10542

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22502 AN: 67916

Other (OTH) AF: 0.300 AC: 630 AN: 2100

Alfa AF: 0.334 Hom.: 1749

Bravo AF: 0.343

Asia WGS AF: 0.366 AC: 1274 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.42
PhyloP100		-0.83
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: rs10889352; hg19: chr1-63099023;