rs142531051

Variant names:

• chr1-62552886-C-T
• rs142531051
• NM_001367561.1:c.2612G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001367561.1(DOCK7):​c.2612G>A​(p.Gly871Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,607,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:6
• Conservation: PhyloP100: 7.61
• 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28811342).

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.2612G>A	p.Gly871Glu	missense	Exon 22 of 50	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.2612G>A	p.Gly871Glu	missense	Exon 22 of 50	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.2612G>A	p.Gly871Glu	missense	Exon 22 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.2612G>A	p.Gly871Glu	missense	Exon 22 of 50	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.2612G>A	p.Gly871Glu	missense	Exon 22 of 49	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.2612G>A	p.Gly871Glu	missense	Exon 22 of 49	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151880 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000125 AC: 31 AN: 248256 AF XY: 0.000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000139 AC: 202 AN: 1455934 Hom.: 0 Cov.: 31 AF XY: 0.000137 AC XY: 99 AN XY: 724280

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25948

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 84972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000177 AC: 196 AN: 1108852

Other (OTH) AF: 0.0000998 AC: 6 AN: 60108

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151880 Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3 AN XY: 74162

African (AFR) AF: 0.0000242 AC: 1 AN: 41310

American (AMR) AF: 0.00 AC: 0 AN: 15230

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000756

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000165 AC: 20

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Developmental and epileptic encephalopathy, 23 (2)
-	2	-	not provided (2)
-	1	-	Inborn genetic diseases (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Benign	0.53
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.073
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.97	N
REVEL	Uncertain	0.31
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.94
MVP		0.75
MPC		0.51
ClinPred		0.35	T
GERP RS		5.0
PromoterAI		0.0038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.64
Mutation Taster		=41/59	disease causing

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: rs142531051; hg19: chr1-63018557;