rs1167998

Variant names:

• chr1-62465961-C-A
• rs1167998
• NM_001367561.1:c.6212+8021G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-62465961-C-A
• chr1-62465961-C-G
• chr1-62465961-C-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.6212+8021G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,028 control chromosomes in the GnomAD database, including 26,855 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 0.58 (26855 hom., cov: 33)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 76 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 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.6212+8021G>T		intron	N/A	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.6185+8021G>T		intron	N/A	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.6179+8021G>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.6212+8021G>T		intron	N/A	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.6179+8021G>T		intron	N/A	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.6206+8021G>T		intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87481 AN: 151910 Hom.: 26850 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.576 AC: 87516 AN: 152028 Hom.: 26855 Cov.: 33 AF XY: 0.578 AC XY: 42930 AN XY: 74304

African (AFR) AF: 0.347 AC: 14365 AN: 41428

American (AMR) AF: 0.608 AC: 9296 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3905 AN: 5172

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4822

European-Finnish (FIN) AF: 0.729 AC: 7702 AN: 10560

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.661 AC: 44921 AN: 67972

Other (OTH) AF: 0.631 AC: 1333 AN: 2112

Alfa AF: 0.637 Hom.: 109233

Bravo AF: 0.559

Asia WGS AF: 0.554 AC: 1926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.31
PhyloP100		0.19
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1167998; hg19: chr1-62931632;