1-62633352-T-C

Position:

• chr1-62633352-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367561.1(DOCK7):​c.1116+146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 586,968 control chromosomes in the GnomAD database, including 32,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8739 hom., cov: 31)
  • Exomes 𝑓: 0.32 (23788 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.828

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-62633352-T-C is Benign according to our data. Variant chr1-62633352-T-C is described in ClinVar as [Benign]. Clinvar id is 1296214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.1116+146A>G		intron_variant		ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.1116+146A>G		intron_variant		5	NM_001367561.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50960 AN: 151770 Hom.: 8728 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.321 AC: 139659 AN: 435078 Hom.: 23788 AF XY: 0.325 AC XY: 75243 AN XY: 231800

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.336 AC: 50999 AN: 151890 Hom.: 8739 Cov.: 31 AF XY: 0.334 AC XY: 24784 AN XY: 74256

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.300

Alfa AF: 0.336 Hom.: 1455

Bravo AF: 0.343

Asia WGS AF: 0.366 AC: 1274 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.42

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: rs10889352; hg19: chr1-63099023;