rs144867736

Variant names:

• chr1-62561695-T-C
• rs144867736
• NM_001367561.1:c.2121A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001367561.1(DOCK7):​c.2121A>G​(p.Leu707Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,562,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: DOCK7 NM_001367561.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-62561695-T-C is Benign according to our data. Variant chr1-62561695-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 475132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.

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.2121A>G	p.Leu707Leu	synonymous	Exon 19 of 50	NP_001354490.1
	DOCK7	NM_001330614.2		c.2121A>G	p.Leu707Leu	synonymous	Exon 19 of 50	NP_001317543.1
	DOCK7	NM_001271999.2		c.2121A>G	p.Leu707Leu	synonymous	Exon 19 of 49	NP_001258928.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK7	ENST00000635253.2	TSL:5 MANE Select	c.2121A>G	p.Leu707Leu	synonymous	Exon 19 of 50	ENSP00000489124.1
	DOCK7	ENST00000454575.6	TSL:1	c.2121A>G	p.Leu707Leu	synonymous	Exon 19 of 49	ENSP00000413583.2
	DOCK7	ENST00000912940.1		c.2121A>G	p.Leu707Leu	synonymous	Exon 19 of 49	ENSP00000582999.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000378 AC: 80 AN: 211710 AF XY: 0.000379

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000585

Gnomad ASJ exome AF: 0.00503

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.000401

GnomAD4 exome AF: 0.000223 AC: 315 AN: 1410226 Hom.: 1 Cov.: 27 AF XY: 0.000237 AC XY: 166 AN XY: 700838

African (AFR) AF: 0.00 AC: 0 AN: 30378

American (AMR) AF: 0.000421 AC: 14 AN: 33288

Ashkenazi Jewish (ASJ) AF: 0.00563 AC: 141 AN: 25036

East Asian (EAS) AF: 0.00 AC: 0 AN: 36978

South Asian (SAS) AF: 0.00 AC: 0 AN: 75402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.000126 AC: 138 AN: 1092582

Other (OTH) AF: 0.000377 AC: 22 AN: 58314

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74408

African (AFR) AF: 0.00 AC: 0 AN: 41536

American (AMR) AF: 0.000262 AC: 4 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68004

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

Alfa AF: 0.000475 Hom.: 0

Bravo AF: 0.000230

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 23 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.30
DANN	Benign	0.68
PhyloP100		-1.7
PromoterAI		-0.0036	Neutral
Mutation Taster		=97/3	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: rs144867736; hg19: chr1-63027366;