rs12042319

chr1-62584148-G-Achr1-62584148-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367561.1(DOCK7):c.1801-894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 976,538 control chromosomes in the GnomAD database, including 61,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9789 hom., cov: 32)
  • Exomes 𝑓: 0.35 (51272 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0950

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-62584148-G-A is Benign according to our data. Variant chr1-62584148-G-A is described in ClinVar as [Benign]. Clinvar id is 1296204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.1801-894C>T		intron_variant		ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.1801-894C>T		intron_variant		5	NM_001367561.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53555 AN: 151802 Hom.: 9776 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.351 AC: 289042 AN: 824618 Hom.: 51272 Cov.: 24 AF XY: 0.351 AC XY: 133844 AN XY: 381056

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.353 AC: 53605 AN: 151920 Hom.: 9789 Cov.: 32 AF XY: 0.350 AC XY: 26029 AN XY: 74272

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.314

Alfa AF: 0.319 Hom.: 2757

Bravo AF: 0.363

Asia WGS AF: 0.367 AC: 1275 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
Cadd	Benign	1.3
Dann	Benign	0.17

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: rs12042319; hg19: chr1-63049819;