1-62455475-G-A

Variant names:

• chr1-62455475-G-A
• rs146910328
• NM_001367561.1:c.6381-19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001367561.1(DOCK7):​c.6381-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,611,920 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (2 hom., cov: 33)
  • Exomes 𝑓: 0.011 (143 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0360
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-62455475-G-A is Benign according to our data. Variant chr1-62455475-G-A is described in ClinVar as [Benign]. Clinvar id is 1590655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00579 (881/152240) while in subpopulation NFE AF = 0.0105 (712/68018). AF 95% confidence interval is 0.00983. There are 2 homozygotes in GnomAd4. There are 386 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.6381-19C>T		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.6381-19C>T		intron_variant	Intron 49 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.00580 AC: 882 AN: 152122 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00548 AC: 1373 AN: 250546 AF XY: 0.00527

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00168

Gnomad NFE exome AF: 0.00989

Gnomad OTH exome AF: 0.00671

GnomAD4 exome AF: 0.0108 AC: 15738 AN: 1459680 Hom.: 143 Cov.: 30 AF XY: 0.0103 AC XY: 7471 AN XY: 726302

African (AFR) AF: 0.00165 AC: 55 AN: 33432

American (AMR) AF: 0.00331 AC: 148 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00150 AC: 129 AN: 86176

European-Finnish (FIN) AF: 0.00192 AC: 102 AN: 53144

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.0133 AC: 14745 AN: 1110434

Other (OTH) AF: 0.00897 AC: 541 AN: 60294

GnomAD4 genome AF: 0.00579 AC: 881 AN: 152240 Hom.: 2 Cov.: 33 AF XY: 0.00519 AC XY: 386 AN XY: 74442

African (AFR) AF: 0.00202 AC: 84 AN: 41536

American (AMR) AF: 0.00294 AC: 45 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

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

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 712 AN: 68018

Other (OTH) AF: 0.00617 AC: 13 AN: 2108

Alfa AF: 0.00728 Hom.: 1

Bravo AF: 0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 23 Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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	-0.57
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.036
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: rs146910328; hg19: chr1-62921146;