Genetic Variant NM_001290223.2:c.3284-15C>T (chr10-127362049-C-T) – 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.3284-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,594,248 control chromosomes in the GnomAD database, including 54,328 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 0.23 ( 4156 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50172 hom. )

Consequence

DOCK1
NM_001290223.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.967

Publications

7 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:

ENSG00000298283 (HGNC:):

ENSG00000298283 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2 link	c.3284-15C>T		intron_variant	Intron 32 of 51	ENST00000623213.2	NP_001277152.2	B2RUU3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DOCK1	ENST00000623213.2 link	c.3284-15C>T	intron_variant	Intron 32 of 51	1	NM_001290223.2	ENSP00000485033.1	A0A096LNH6
DOCK1	ENST00000280333.9 link	c.3221-15C>T	intron_variant	Intron 32 of 51	1		ENSP00000280333.6	Q14185
ENSG00000298283	ENST00000754441.1 link	n.722G>A	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35188

AN:

151996

Hom.:

4148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.232

AC:

53825

AN:

231856

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.261

AC:

376501

AN:

1442134

Hom.:

50172

Cov.:

AF XY:

0.262

AC XY:

187389

AN XY:

716276

show subpopulations

African (AFR)

AF:

0.183

AC:

5945

AN:

32442

American (AMR)

AF:

0.115

AC:

4693

AN:

40972

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

5199

AN:

25432

East Asian (EAS)

AF:

0.281

AC:

11094

AN:

39440

South Asian (SAS)

AF:

0.283

AC:

23422

AN:

82750

European-Finnish (FIN)

AF:

0.244

AC:

12935

AN:

53010

Middle Eastern (MID)

AF:

0.201

AC:

1140

AN:

5658

European-Non Finnish (NFE)

AF:

0.269

AC:

297154

AN:

1102908

Other (OTH)

AF:

0.251

AC:

14919

AN:

59522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

12349

24698

37047

49396

61745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10002

20004

30006

40008

50010

<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:

0.232

AC:

35215

AN:

152114

Hom.:

4156

Cov.:

AF XY:

0.232

AC XY:

17285

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.194

AC:

8050

AN:

41502

American (AMR)

AF:

0.174

AC:

2661

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

709

AN:

3472

East Asian (EAS)

AF:

0.253

AC:

1309

AN:

5168

South Asian (SAS)

AF:

0.285

AC:

1374

AN:

4826

European-Finnish (FIN)

AF:

0.240

AC:

2530

AN:

10556

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17915

AN:

67992

Other (OTH)

AF:

0.238

AC:

502

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1425

2850

4276

5701

7126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.246

Hom.:

7800

Bravo

AF:

0.220

Asia WGS

AF:

0.279

AC:

971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.0

(source)

DANN

Benign

0.27

PhyloP100

0.97

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