1-62584148-G-C

Variant names:

• chr1-62584148-G-C
• rs12042319
• NM_001367561.1:c.1801-894C>G

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.1801-894C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000241 in 828,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 24 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1801-894C>G		intron_variant	Intron 15 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1801-894C>G		intron_variant	Intron 15 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000241 AC: 2 AN: 828832 Hom.: 0 Cov.: 24 AF XY: 0.00000261 AC XY: 1 AN XY: 382930

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15676

American (AMR) AF: 0.00 AC: 0 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5126

East Asian (EAS) AF: 0.00 AC: 0 AN: 3618

South Asian (SAS) AF: 0.00 AC: 0 AN: 16352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1612

European-Non Finnish (NFE) AF: 0.00000264 AC: 2 AN: 758020

Other (OTH) AF: 0.00 AC: 0 AN: 27170

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		0.095

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: rs12042319; hg19: chr1-63049819;