NM_001367561.1:c.*155C>T

Variant names:

• chr1-62455259-G-A
• rs79913813
• NM_001367561.1:c.*155C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001367561.1(DOCK7):​c.*155C>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 0.000543 in 801,216 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (5 hom.)
• Consequence: DOCK7 NM_001367561.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.106
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.063).
• BP6: Variant 1-62455259-G-A is Benign according to our data. Variant chr1-62455259-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2430657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000407 (62/152246) while in subpopulation EAS AF = 0.00983 (51/5188). AF 95% confidence interval is 0.00768. There are 1 homozygotes in GnomAd4. There are 35 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.*155C>T		3_prime_UTR	Exon 50 of 50	NP_001354490.1	Q96N67-1
	DOCK7	NM_001330614.2		c.*155C>T		3_prime_UTR	Exon 50 of 50	NP_001317543.1	Q96N67-6
	DOCK7	NM_001271999.2		c.*155C>T		3_prime_UTR	Exon 49 of 49	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.*155C>T		3_prime_UTR	Exon 50 of 50	ENSP00000489124.1	Q96N67-1
	DOCK7	ENST00000454575.6	TSL:1	c.*155C>T		3_prime_UTR	Exon 49 of 49	ENSP00000413583.2	Q96N67-2
	DOCK7	ENST00000912940.1		c.*155C>T		3_prime_UTR	Exon 49 of 49	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 62 AN: 152128 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00981

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000971 AC: 139 AN: 143120 AF XY: 0.00108

Gnomad AFR exome AF: 0.000128

Gnomad AMR exome AF: 0.000165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0119

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000236

GnomAD4 exome AF: 0.000575 AC: 373 AN: 648970 Hom.: 5 Cov.: 8 AF XY: 0.000579 AC XY: 200 AN XY: 345560

African (AFR) AF: 0.0000576 AC: 1 AN: 17368

American (AMR) AF: 0.000116 AC: 4 AN: 34386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20518

East Asian (EAS) AF: 0.0106 AC: 344 AN: 32422

South Asian (SAS) AF: 0.0000469 AC: 3 AN: 63974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4228

European-Non Finnish (NFE) AF: 0.0000197 AC: 8 AN: 406234

Other (OTH) AF: 0.000384 AC: 13 AN: 33888

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152246 Hom.: 1 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74428

African (AFR) AF: 0.000168 AC: 7 AN: 41546

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00983 AC: 51 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000499

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.11
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: rs79913813; hg19: chr1-62920930; COSMIC: COSV52018754; COSMIC: COSV52018754;