rs882052

Positions:

• chr10-127043306-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290223.2(DOCK1):​c.2201+142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 671,368 control chromosomes in the GnomAD database, including 44,459 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 0.36 (10033 hom., cov: 33)
  • Exomes 𝑓: 0.36 (34426 hom.)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2201+142T>C		intron_variant		ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2201+142T>C		intron_variant		1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.2138+142T>C		intron_variant		1		ENSP00000280333	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54975 AN: 151946 Hom.: 10019 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.359 AC: 186216 AN: 519304 Hom.: 34426 AF XY: 0.355 AC XY: 98420 AN XY: 277574

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.362 AC: 55023 AN: 152064 Hom.: 10033 Cov.: 33 AF XY: 0.360 AC XY: 26788 AN XY: 74334

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.384

Alfa AF: 0.359 Hom.: 4597

Bravo AF: 0.372

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.82

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: rs882052; hg19: chr10-128841570;