1-62455318-C-A

Variant names:

• chr1-62455318-C-A
• rs114747052
• NM_001367561.1:c.*96G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The NM_001367561.1(DOCK7):​c.*96G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 1,323,122 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (4 hom.)
• Consequence: DOCK7 NM_001367561.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.29).
• BP6: Variant 1-62455318-C-A is Benign according to our data. Variant chr1-62455318-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1327699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00298 (454/152238) while in subpopulation AFR AF = 0.0104 (430/41546). AF 95% confidence interval is 0.00954. There are 0 homozygotes in GnomAd4. There are 214 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.*96G>T		3_prime_UTR_variant	Exon 50 of 50	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.*96G>T		3_prime_UTR_variant	Exon 50 of 50	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 453 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000750 AC: 161 AN: 214778 AF XY: 0.000541

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000345

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000105

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.000318 AC: 372 AN: 1170884 Hom.: 4 Cov.: 16 AF XY: 0.000293 AC XY: 174 AN XY: 594726

African (AFR) AF: 0.0113 AC: 305 AN: 27108

American (AMR) AF: 0.000428 AC: 18 AN: 42032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24278

East Asian (EAS) AF: 0.00 AC: 0 AN: 36792

South Asian (SAS) AF: 0.0000257 AC: 2 AN: 77766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47762

Middle Eastern (MID) AF: 0.000191 AC: 1 AN: 5222

European-Non Finnish (NFE) AF: 0.0000151 AC: 13 AN: 859004

Other (OTH) AF: 0.000648 AC: 33 AN: 50920

GnomAD4 genome AF: 0.00298 AC: 454 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.00288 AC XY: 214 AN XY: 74426

African (AFR) AF: 0.0103 AC: 430 AN: 41546

American (AMR) AF: 0.00105 AC: 16 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68002

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00159 Hom.: 0

Bravo AF: 0.00350

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 12, 2021

GeneDx

Significance: Likely 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	-0.58
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs114747052; hg19: chr1-62920989;