NM_001367561.1:c.1283-14delT

Variant names:

• chr1-62625414-TA-T
• rs541344421
• NM_001367561.1:c.1283-14delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001367561.1(DOCK7):​c.1283-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 1,515,688 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (50 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.26
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-62625414-TA-T is Benign according to our data. Variant chr1-62625414-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235780.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 = 0.00533 (804/150782) while in subpopulation NFE AF = 0.00827 (559/67568). AF 95% confidence interval is 0.00771. There are 2 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	NM_001367561.1	MANE Select	c.1283-14delT		intron	N/A	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.1283-14delT		intron	N/A	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.1283-14delT		intron	N/A	NP_001258928.1	Q96N67-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.1283-14delT		intron	N/A	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.1283-14delT		intron	N/A	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.1283-14delT		intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 804 AN: 150676 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00163

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00410

Gnomad ASJ AF: 0.00581

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000838

Gnomad FIN AF: 0.00798

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00827

Gnomad OTH AF: 0.00435

GnomAD2 exomes AF: 0.00659 AC: 1234 AN: 187348 AF XY: 0.00682

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00832

Gnomad EAS exome AF: 0.000975

Gnomad FIN exome AF: 0.00816

Gnomad NFE exome AF: 0.00956

Gnomad OTH exome AF: 0.00983

GnomAD4 exome AF: 0.00839 AC: 11457 AN: 1364906 Hom.: 50 Cov.: 30 AF XY: 0.00822 AC XY: 5559 AN XY: 676582

African (AFR) AF: 0.00174 AC: 52 AN: 29918

American (AMR) AF: 0.00243 AC: 81 AN: 33350

Ashkenazi Jewish (ASJ) AF: 0.00644 AC: 149 AN: 23154

East Asian (EAS) AF: 0.000320 AC: 12 AN: 37444

South Asian (SAS) AF: 0.00132 AC: 99 AN: 75018

European-Finnish (FIN) AF: 0.00789 AC: 396 AN: 50182

Middle Eastern (MID) AF: 0.000752 AC: 4 AN: 5316

European-Non Finnish (NFE) AF: 0.00974 AC: 10270 AN: 1054634

Other (OTH) AF: 0.00705 AC: 394 AN: 55890

GnomAD4 genome AF: 0.00533 AC: 804 AN: 150782 Hom.: 2 Cov.: 32 AF XY: 0.00500 AC XY: 368 AN XY: 73618

African (AFR) AF: 0.00163 AC: 67 AN: 41168

American (AMR) AF: 0.00410 AC: 62 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00581 AC: 20 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000839 AC: 4 AN: 4768

European-Finnish (FIN) AF: 0.00798 AC: 82 AN: 10276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00827 AC: 559 AN: 67568

Other (OTH) AF: 0.00431 AC: 9 AN: 2090

Alfa AF: 0.00504 Hom.: 0

Bravo AF: 0.00499

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Developmental and epileptic encephalopathy, 23 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.3
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: rs541344421; hg19: chr1-63091085; COSMIC: COSV52017611; COSMIC: COSV52017611;