dbSNP rs2498947: DOCK1:c.3044+14892G>A (chr10-127272321-G-A) – 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.3044+14892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,100 control chromosomes in the GnomAD database, including 7,110 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 0.27 ( 7109 hom., cov: 33)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

DOCK1
NM_001290223.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

2 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2 link	c.3044+14892G>A		intron_variant	Intron 29 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DOCK1	ENST00000623213.2 link	c.3044+14892G>A	intron_variant	Intron 29 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9 link	c.2981+14892G>A	intron_variant	Intron 29 of 51	1		ENSP00000280333.6
DOCK1	ENST00000484400.5 link	n.197+14892G>A	intron_variant	Intron 2 of 4	3
DOCK1	ENST00000464466.1 link	n.*125G>A	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41621

AN:

151980

Hom.:

7112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<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:

0.274

AC:

41618

AN:

152098

Hom.:

7109

Cov.:

AF XY:

0.277

AC XY:

20592

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0694

AC:

2882

AN:

41522

American (AMR)

AF:

0.337

AC:

5140

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1426

AN:

3466

East Asian (EAS)

AF:

0.232

AC:

1198

AN:

5164

South Asian (SAS)

AF:

0.518

AC:

2495

AN:

4818

European-Finnish (FIN)

AF:

0.294

AC:

3116

AN:

10582

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24195

AN:

67956

Other (OTH)

AF:

0.307

AC:

649

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1406

2811

4217

5622

7028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.330

Hom.:

4949

Bravo

AF:

0.267

Asia WGS

AF:

0.309

AC:

1077

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.3

(source)

DANN

Benign

0.71

PhyloP100

1.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over