rs12048208

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.1683-2985C>T		intron_variant		ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.1683-2985C>T		intron_variant		5	NM_001367561.1

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0895

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.125

Alfa AF: 0.125 Hom.: 2567

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12048208; hg19: chr1-63055280;