1-62633352-T-A

Variant names:

• chr1-62633352-T-A
• rs10889352
• NM_001367561.1:c.1116+146A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367561.1(DOCK7):​c.1116+146A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.1116+146A>T		intron	N/A	NP_001354490.1
	DOCK7	NM_001330614.2		c.1116+146A>T		intron	N/A	NP_001317543.1
	DOCK7	NM_001271999.2		c.1116+146A>T		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.1116+146A>T		intron	N/A	ENSP00000489124.1
	DOCK7	ENST00000454575.6	TSL:1	c.1116+146A>T		intron	N/A	ENSP00000413583.2
	DOCK7	ENST00000912940.1		c.1116+146A>T		intron	N/A	ENSP00000582999.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 435948 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 232250

African (AFR) AF: 0.00 AC: 0 AN: 11354

American (AMR) AF: 0.00 AC: 0 AN: 19286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12338

East Asian (EAS) AF: 0.00 AC: 0 AN: 29598

South Asian (SAS) AF: 0.00 AC: 0 AN: 30498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 270802

Other (OTH) AF: 0.00 AC: 0 AN: 24370

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1749

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.29
PhyloP100		-0.83

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: rs10889352; hg19: chr1-63099023;