10-127027748-A-G

Variant names:

• chr10-127027748-A-G
• rs4615933
• NM_001290223.2:c.1624+1324A>G

Variant summary

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

The NM_001290223.2(DOCK1):​c.1624+1324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,494 control chromosomes in the GnomAD database, including 8,539 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 0.33 (8539 hom., cov: 31)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 2 publications found

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.1624+1324A>G		intron_variant	Intron 16 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.1624+1324A>G		intron_variant	Intron 16 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.1561+1324A>G		intron_variant	Intron 16 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50478 AN: 151374 Hom.: 8536 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.333 AC: 50514 AN: 151494 Hom.: 8539 Cov.: 31 AF XY: 0.329 AC XY: 24325 AN XY: 74006

African (AFR) AF: 0.315 AC: 12957 AN: 41074

American (AMR) AF: 0.347 AC: 5297 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3466

East Asian (EAS) AF: 0.173 AC: 887 AN: 5122

South Asian (SAS) AF: 0.468 AC: 2253 AN: 4810

European-Finnish (FIN) AF: 0.242 AC: 2543 AN: 10520

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24317 AN: 67920

Other (OTH) AF: 0.359 AC: 753 AN: 2100

Alfa AF: 0.343 Hom.: 10667

Bravo AF: 0.335

Asia WGS AF: 0.308 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.43
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: rs4615933; hg19: chr10-128826012; COSMIC: COSV54758913; COSMIC: COSV54758913;