rs1748195

Positions:

• chr1-62583922-C-G
• chr1-62583922-C-T

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.1801-668G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,976 control chromosomes in the GnomAD database, including 15,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (15252 hom., cov: 33)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0810

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=-0.91).
• BP6: Variant 1-62583922-C-G is Benign according to our data. Variant chr1-62583922-C-G is described in ClinVar as [Benign]. Clinvar id is 1251405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.1801-668G>C		intron_variant		ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.1801-668G>C		intron_variant		5	NM_001367561.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63848 AN: 151858 Hom.: 15209 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.421 AC: 63953 AN: 151976 Hom.: 15252 Cov.: 33 AF XY: 0.418 AC XY: 31063 AN XY: 74292

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.367

Alfa AF: 0.341 Hom.: 5143

Bravo AF: 0.439

Asia WGS AF: 0.440 AC: 1526 AN: 3466

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 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.36

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: rs1748195; hg19: chr1-63049593;