1-62584927-T-G

Variant names:

• chr1-62584927-T-G
• rs3850634
• NM_001367561.1:c.1800+1580A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367561.1(DOCK7):​c.1800+1580A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 679,296 control chromosomes in the GnomAD database, including 37,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8662 hom., cov: 31)
  • Exomes 𝑓: 0.32 (28987 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.532
• Publications: 31 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=-0.52).
• BP6: Variant 1-62584927-T-G is Benign according to our data. Variant chr1-62584927-T-G is described in ClinVar as Benign. ClinVar VariationId is 1227339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367561.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	NM_001367561.1	MANE Select	c.1800+1580A>C		intron	N/A	NP_001354490.1
	DOCK7	NM_001330614.2		c.1800+1580A>C		intron	N/A	NP_001317543.1
	DOCK7	NM_001271999.2		c.1800+1580A>C		intron	N/A	NP_001258928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.1800+1580A>C		intron	N/A	ENSP00000489124.1
	DOCK7	ENST00000454575.6	TSL:1	c.1800+1580A>C		intron	N/A	ENSP00000413583.2
	DOCK7	ENST00000912940.1		c.1800+1580A>C		intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50754 AN: 151754 Hom.: 8651 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.328 AC: 39898 AN: 121514 AF XY: 0.335

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.370

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.198

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.322 AC: 170043 AN: 527424 Hom.: 28987 Cov.: 0 AF XY: 0.329 AC XY: 93781 AN XY: 285256

African (AFR) AF: 0.372 AC: 5107 AN: 13746

American (AMR) AF: 0.361 AC: 9488 AN: 26290

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 4099 AN: 18112

East Asian (EAS) AF: 0.161 AC: 5032 AN: 31288

South Asian (SAS) AF: 0.434 AC: 24472 AN: 56328

European-Finnish (FIN) AF: 0.259 AC: 12143 AN: 46876

Middle Eastern (MID) AF: 0.273 AC: 1039 AN: 3812

European-Non Finnish (NFE) AF: 0.329 AC: 99473 AN: 302090

Other (OTH) AF: 0.318 AC: 9190 AN: 28882

GnomAD4 genome AF: 0.334 AC: 50792 AN: 151872 Hom.: 8662 Cov.: 31 AF XY: 0.332 AC XY: 24683 AN XY: 74250

African (AFR) AF: 0.378 AC: 15651 AN: 41382

American (AMR) AF: 0.336 AC: 5136 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3466

East Asian (EAS) AF: 0.189 AC: 977 AN: 5164

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4812

European-Finnish (FIN) AF: 0.249 AC: 2635 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22487 AN: 67906

Other (OTH) AF: 0.299 AC: 631 AN: 2108

Alfa AF: 0.337 Hom.: 5722

Bravo AF: 0.342

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		0.53
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: rs3850634; hg19: chr1-63050598; COSMIC: COSV107235189;