1-62455751-T-C

Variant names:

• chr1-62455751-T-C
• rs634341
• NM_001367561.1:c.6381-295A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367561.1(DOCK7):​c.6381-295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,018 control chromosomes in the GnomAD database, including 15,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (15148 hom., cov: 32)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.768
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-62455751-T-C is Benign according to our data. Variant chr1-62455751-T-C is described in ClinVar as [Benign]. Clinvar id is 1264632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.6381-295A>G		intron_variant	Intron 49 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.6381-295A>G		intron_variant	Intron 49 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63729 AN: 151900 Hom.: 15119 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.420 AC: 63812 AN: 152018 Hom.: 15148 Cov.: 32 AF XY: 0.417 AC XY: 30976 AN XY: 74326

African (AFR) AF: 0.653 AC: 27066 AN: 41442

American (AMR) AF: 0.390 AC: 5953 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1269 AN: 5168

South Asian (SAS) AF: 0.450 AC: 2161 AN: 4806

European-Finnish (FIN) AF: 0.249 AC: 2638 AN: 10580

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22674 AN: 67958

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.385 Hom.: 2798

Bravo AF: 0.438

Asia WGS AF: 0.443 AC: 1542 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		-0.77
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: rs634341; hg19: chr1-62921422;