dbSNP rs882052: DOCK1:c.2201+142T>C (chr10-127043306-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.655

Publications

4 publications found

Variant links:

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]

DOCK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290223.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK1	NM_001290223.2	MANE Select	c.2201+142T>C	intron	N/A	NP_001277152.2	A0A096LNH6
DOCK1	NM_001377543.1		c.2138+142T>C	intron	N/A	NP_001364472.1
DOCK1	NM_001377544.1		c.2174+142T>C	intron	N/A	NP_001364473.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK1	ENST00000623213.2	TSL:1 MANE Select	c.2201+142T>C	intron	N/A	ENSP00000485033.1	A0A096LNH6
DOCK1	ENST00000280333.9	TSL:1	c.2138+142T>C	intron	N/A	ENSP00000280333.6	Q14185
DOCK1	ENST00000939683.1		c.2201+142T>C	intron	N/A	ENSP00000609742.1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54975

AN:

151946

Hom.:

10019

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.351

AC:

4381

AN:

12486

American (AMR)

AF:

0.416

AC:

6781

AN:

16292

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

5632

AN:

16626

East Asian (EAS)

AF:

0.421

AC:

12696

AN:

30178

South Asian (SAS)

AF:

0.287

AC:

14290

AN:

49812

European-Finnish (FIN)

AF:

0.371

AC:

15559

AN:

41966

Middle Eastern (MID)

AF:

0.351

AC:

836

AN:

2382

European-Non Finnish (NFE)

AF:

0.360

AC:

115755

AN:

321462

Other (OTH)

AF:

0.366

AC:

10286

AN:

28100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5569

11138

16706

22275

27844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1000

2000

3000

4000

5000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.362

AC:

55023

AN:

152064

Hom.:

10033

Cov.:

AF XY:

0.360

AC XY:

26788

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.351

AC:

14534

AN:

41466

American (AMR)

AF:

0.407

AC:

6226

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1160

AN:

3472

East Asian (EAS)

AF:

0.393

AC:

2026

AN:

5160

South Asian (SAS)

AF:

0.286

AC:

1380

AN:

4820

European-Finnish (FIN)

AF:

0.354

AC:

3746

AN:

10580

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24674

AN:

67966

Other (OTH)

AF:

0.384

AC:

811

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1824

3647

5471

7294

9118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.360

Hom.:

5183

Bravo

AF:

0.372

Asia WGS

AF:

0.374

AC:

1300

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over