1-62504726-C-T

Variant names:

• chr1-62504726-C-T
• rs115353638
• NM_001367561.1:c.4668G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001367561.1(DOCK7):​c.4668G>A​(p.Arg1556Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,056 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: DOCK7 NM_001367561.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.130
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.057).
• BP6: Variant 1-62504726-C-T is Benign according to our data. Variant chr1-62504726-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.13 with no splicing effect.

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.4668G>A	p.Arg1556Arg	synonymous	Exon 37 of 50	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.4641G>A	p.Arg1547Arg	synonymous	Exon 37 of 50	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.4641G>A	p.Arg1547Arg	synonymous	Exon 37 of 49	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.4668G>A	p.Arg1556Arg	synonymous	Exon 37 of 50	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.4641G>A	p.Arg1547Arg	synonymous	Exon 37 of 49	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.4668G>A	p.Arg1556Arg	synonymous	Exon 37 of 49	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000859 AC: 216 AN: 251322 AF XY: 0.000905

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00142 AC: 2073 AN: 1461812 Hom.: 1 Cov.: 30 AF XY: 0.00143 AC XY: 1042 AN XY: 727204

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86256

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53406

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.00172 AC: 1912 AN: 1111976

Other (OTH) AF: 0.00101 AC: 61 AN: 60390

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152244 Hom.: 1 Cov.: 32 AF XY: 0.000914 AC XY: 68 AN XY: 74432

African (AFR) AF: 0.000193 AC: 8 AN: 41524

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68030

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00150 Hom.: 1

Bravo AF: 0.000963

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Developmental and epileptic encephalopathy, 23 (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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: rs115353638; hg19: chr1-62970397;