rs17123688

Variant names:

• chr1-62510677-T-C
• rs17123688
• NM_001367561.1:c.4283-4A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-62510677-T-C
• chr1-62510677-T-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.4283-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,610,796 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (254 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (433 hom.)
• Consequence: DOCK7 NM_001367561.1 splice_region, intron
• Scores: Splicing: ADA: 0.009862
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.321
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-62510677-T-C is Benign according to our data. Variant chr1-62510677-T-C is described in ClinVar as Benign. ClinVar VariationId is 475145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.4283-4A>G		splice_region intron	N/A	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.4256-4A>G		splice_region intron	N/A	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.4256-4A>G		splice_region 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.4283-4A>G		splice_region intron	N/A	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.4256-4A>G		splice_region intron	N/A	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.4283-4A>G		splice_region intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5569 AN: 152146 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.0277

GnomAD2 exomes AF: 0.0186 AC: 4650 AN: 249428 AF XY: 0.0167

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0242

Gnomad ASJ exome AF: 0.00798

Gnomad EAS exome AF: 0.0486

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00130

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00854 AC: 12455 AN: 1458532 Hom.: 433 Cov.: 29 AF XY: 0.00881 AC XY: 6391 AN XY: 725602

African (AFR) AF: 0.114 AC: 3802 AN: 33312

American (AMR) AF: 0.0257 AC: 1140 AN: 44302

Ashkenazi Jewish (ASJ) AF: 0.00798 AC: 208 AN: 26050

East Asian (EAS) AF: 0.0627 AC: 2478 AN: 39550

South Asian (SAS) AF: 0.0292 AC: 2504 AN: 85722

European-Finnish (FIN) AF: 0.000450 AC: 24 AN: 53322

Middle Eastern (MID) AF: 0.0108 AC: 62 AN: 5756

European-Non Finnish (NFE) AF: 0.00125 AC: 1390 AN: 1110276

Other (OTH) AF: 0.0141 AC: 847 AN: 60242

GnomAD4 genome AF: 0.0367 AC: 5591 AN: 152264 Hom.: 254 Cov.: 32 AF XY: 0.0372 AC XY: 2766 AN XY: 74444

African (AFR) AF: 0.106 AC: 4412 AN: 41532

American (AMR) AF: 0.0354 AC: 542 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.0537 AC: 278 AN: 5178

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00166 AC: 113 AN: 68028

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0160 Hom.: 73

Bravo AF: 0.0407

Asia WGS AF: 0.0650 AC: 224 AN: 3474

EpiCase AF: 0.00137

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Developmental and epileptic encephalopathy, 23 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.4
DANN	Benign	0.65
PhyloP100		0.32
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0099
dbscSNV1_RF	Benign	0.29
SpliceAI score (max)		0.010		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: rs17123688; hg19: chr1-62976348; COSMIC: COSV51999716;