1-62596235-C-T

Position:

• chr1-62596235-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367561.1(DOCK7):​c.1683-9611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,876 control chromosomes in the GnomAD database, including 12,457 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 0.39 (12457 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.1683-9611G>A		intron_variant		ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.1683-9611G>A		intron_variant		5	NM_001367561.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59226 AN: 151758 Hom.: 12432 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.390 AC: 59301 AN: 151876 Hom.: 12457 Cov.: 31 AF XY: 0.389 AC XY: 28843 AN XY: 74220

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.342

Alfa AF: 0.375 Hom.: 1939

Bravo AF: 0.405

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs11207997; hg19: chr1-63061906;