chr1-62560271-G-T

Variant names:

• chr1-62560271-G-T
• rs2131925
• NM_001367561.1:c.2200-1051C>A

Variant summary

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

The NM_001367561.1(DOCK7):​c.2200-1051C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,992 control chromosomes in the GnomAD database, including 27,295 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 0.58 (27295 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 127 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.2200-1051C>A		intron_variant	Intron 19 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.2200-1051C>A		intron_variant	Intron 19 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88025 AN: 151874 Hom.: 27298 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 88038 AN: 151992 Hom.: 27295 Cov.: 31 AF XY: 0.582 AC XY: 43225 AN XY: 74292

African (AFR) AF: 0.344 AC: 14242 AN: 41430

American (AMR) AF: 0.609 AC: 9292 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2635 AN: 3468

East Asian (EAS) AF: 0.757 AC: 3910 AN: 5164

South Asian (SAS) AF: 0.546 AC: 2634 AN: 4822

European-Finnish (FIN) AF: 0.750 AC: 7935 AN: 10574

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45299 AN: 67948

Other (OTH) AF: 0.634 AC: 1338 AN: 2110

Alfa AF: 0.643 Hom.: 108797

Bravo AF: 0.561

Asia WGS AF: 0.560 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs2131925; hg19: chr1-63025942;