rs1748197

Variant names:

• chr1-62590441-G-A
• rs1748197
• NM_001367561.1:c.1683-3817C>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.1683-3817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,018 control chromosomes in the GnomAD database, including 15,009 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 0.42 (15009 hom., cov: 32)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1683-3817C>T		intron_variant	Intron 14 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1683-3817C>T		intron_variant	Intron 14 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63204 AN: 151900 Hom.: 14967 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.416 AC: 63306 AN: 152018 Hom.: 15009 Cov.: 32 AF XY: 0.413 AC XY: 30681 AN XY: 74292

African (AFR) AF: 0.654 AC: 27131 AN: 41464

American (AMR) AF: 0.367 AC: 5600 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3466

East Asian (EAS) AF: 0.211 AC: 1095 AN: 5178

South Asian (SAS) AF: 0.451 AC: 2168 AN: 4802

European-Finnish (FIN) AF: 0.249 AC: 2633 AN: 10560

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22635 AN: 67952

Other (OTH) AF: 0.361 AC: 764 AN: 2116

Alfa AF: 0.372 Hom.: 15416

Bravo AF: 0.433

Asia WGS AF: 0.425 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.41
PhyloP100		-0.30
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: rs1748197; hg19: chr1-63056112;