rs4350231

Variant names:

• chr1-62456989-G-A
• rs4350231
• NM_001367561.1:c.6380+549C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367561.1(DOCK7):​c.6380+549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,896 control chromosomes in the GnomAD database, including 8,485 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8485 hom., cov: 32)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 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.6380+549C>T		intron	N/A	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.6353+549C>T		intron	N/A	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.6347+549C>T		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.6380+549C>T		intron	N/A	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.6347+549C>T		intron	N/A	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.6374+549C>T		intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50392 AN: 151778 Hom.: 8476 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.332 AC: 50426 AN: 151896 Hom.: 8485 Cov.: 32 AF XY: 0.332 AC XY: 24625 AN XY: 74246

African (AFR) AF: 0.352 AC: 14585 AN: 41426

American (AMR) AF: 0.336 AC: 5133 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3468

East Asian (EAS) AF: 0.191 AC: 989 AN: 5166

South Asian (SAS) AF: 0.427 AC: 2054 AN: 4808

European-Finnish (FIN) AF: 0.272 AC: 2865 AN: 10524

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22915 AN: 67948

Other (OTH) AF: 0.299 AC: 630 AN: 2104

Alfa AF: 0.335 Hom.: 3013

Bravo AF: 0.335

Asia WGS AF: 0.369 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		1.2
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: rs4350231; hg19: chr1-62922660;