1-62454337-A-G

Variant names:

• chr1-62454337-A-G
• rs636523
• ENST00000634495.2:n.3639T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000634495.2(DOCK7):​n.3639T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,902 control chromosomes in the GnomAD database, including 10,340 homozygotes. 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: 𝑓 0.36 (10340 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: DOCK7 ENST00000634495.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000634495.2	n.3639T>C		non_coding_transcript_exon_variant	Exon 8 of 8	5

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54734 AN: 151766 Hom.: 10329 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.167 AC: 3 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.214 AC: 3 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.361 AC: 54773 AN: 151884 Hom.: 10340 Cov.: 31 AF XY: 0.358 AC XY: 26582 AN XY: 74250

African (AFR) AF: 0.469 AC: 19413 AN: 41378

American (AMR) AF: 0.346 AC: 5270 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3472

East Asian (EAS) AF: 0.193 AC: 996 AN: 5170

South Asian (SAS) AF: 0.420 AC: 2018 AN: 4808

European-Finnish (FIN) AF: 0.249 AC: 2623 AN: 10544

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.331 AC: 22528 AN: 67966

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.353 Hom.: 3840

Bravo AF: 0.372

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.0
DANN	Benign	0.77
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs636523; hg19: chr1-62920008;