NM_001367561.1:c.468A>G

Variant names:

• chr1-62648466-T-C
• rs750226687
• NM_001367561.1:c.468A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001367561.1(DOCK7):​c.468A>G​(p.Gln156Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,546,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.572
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-62648466-T-C is Benign according to our data. Variant chr1-62648466-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 571256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.572 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	NM_001367561.1	MANE Select	c.468A>G	p.Gln156Gln	synonymous	Exon 5 of 50	NP_001354490.1
	DOCK7	NM_001330614.2		c.468A>G	p.Gln156Gln	synonymous	Exon 5 of 50	NP_001317543.1
	DOCK7	NM_001271999.2		c.468A>G	p.Gln156Gln	synonymous	Exon 5 of 49	NP_001258928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.468A>G	p.Gln156Gln	synonymous	Exon 5 of 50	ENSP00000489124.1
	DOCK7	ENST00000454575.6	TSL:1	c.468A>G	p.Gln156Gln	synonymous	Exon 5 of 49	ENSP00000413583.2
	DOCK7	ENST00000251157.10	TSL:5	c.468A>G	p.Gln156Gln	synonymous	Exon 5 of 50	ENSP00000251157.6

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000950 AC: 19 AN: 200008 AF XY: 0.000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.000201

GnomAD4 exome AF: 0.000181 AC: 252 AN: 1394492 Hom.: 0 Cov.: 31 AF XY: 0.000179 AC XY: 124 AN XY: 690886

African (AFR) AF: 0.0000322 AC: 1 AN: 31054

American (AMR) AF: 0.0000998 AC: 4 AN: 40078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24778

East Asian (EAS) AF: 0.00 AC: 0 AN: 36670

South Asian (SAS) AF: 0.00 AC: 0 AN: 74142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4358

European-Non Finnish (NFE) AF: 0.000225 AC: 242 AN: 1076346

Other (OTH) AF: 0.0000878 AC: 5 AN: 56930

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152134 Hom.: 1 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74330

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00138 AC: 21 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000159 Hom.: 0

Bravo AF: 0.000268

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 23 Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.7
DANN	Benign	0.36
PhyloP100		0.57
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: rs750226687; hg19: chr1-63114137; COSMIC: COSV99226764; COSMIC: COSV99226764;