rs12048208

Variant names:

• chr1-62589609-G-A
• rs12048208
• NM_001367561.1:c.1683-2985C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-62589609-G-A
• chr1-62589609-G-T

Variant summary

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

The NM_001367561.1(DOCK7):​c.1683-2985C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,224 control chromosomes in the GnomAD database, including 1,291 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 0.13 (1291 hom., cov: 31)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1683-2985C>T		intron_variant	Intron 14 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1683-2985C>T		intron_variant	Intron 14 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 18996 AN: 151110 Hom.: 1285 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0895

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.126 AC: 19022 AN: 151224 Hom.: 1291 Cov.: 31 AF XY: 0.126 AC XY: 9294 AN XY: 73812

African (AFR) AF: 0.122 AC: 5014 AN: 41232

American (AMR) AF: 0.111 AC: 1687 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 310 AN: 3462

East Asian (EAS) AF: 0.178 AC: 918 AN: 5148

South Asian (SAS) AF: 0.254 AC: 1218 AN: 4788

European-Finnish (FIN) AF: 0.0894 AC: 918 AN: 10266

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8470 AN: 67828

Other (OTH) AF: 0.125 AC: 262 AN: 2096

Alfa AF: 0.126 Hom.: 4070

Bravo AF: 0.126

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.44
DANN	Benign	0.48
PhyloP100		-0.34
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: rs12048208; hg19: chr1-63055280;