dbSNP rs700241: DAB2:p.Thr586Ile (chr5-39377030-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_001343.4(DAB2):c.1757C>T(p.Thr586Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,614,058 control chromosomes in the GnomAD database, including 797 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.044 ( 329 hom., cov: 32)

Exomes 𝑓: 0.016 ( 468 hom. )

Consequence

DAB2
NM_001343.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

Publications

14 publications found

Variant links:

Genes affected

DAB2 (HGNC:2662): (DAB adaptor protein 2) This gene encodes a mitogen-responsive phosphoprotein. It is expressed in normal ovarian epithelial cells, but is down-regulated or absent from ovarian carcinoma cell lines, suggesting its role as a tumor suppressor. This protein binds to the SH3 domains of GRB2, an adaptor protein that couples tyrosine kinase receptors to SOS (a guanine nucleotide exchange factor for Ras), via its C-terminal proline-rich sequences, and may thus modulate growth factor/Ras pathways by competing with SOS for binding to GRB2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

DAB2 links:

ENSG00000289699 (HGNC:):

ENSG00000289699 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 (MetaRNN=0.0017542243).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB2	NM_001343.4 link	c.1757C>T	p.Thr586Ile	missense_variant	Exon 12 of 15	ENST00000320816.11	NP_001334.2	P98082-1A0A024R036B2RAW0
DAB2	NM_001244871.2 link	c.1694C>T	p.Thr565Ile	missense_variant	Exon 11 of 14		NP_001231800.1	P98082-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11 link	c.1757C>T	p.Thr586Ile	missense_variant	Exon 12 of 15	1	NM_001343.4	ENSP00000313391.6		P98082-1

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6658

AN:

152074

Hom.:

328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0385

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0345

GnomAD2 exomes

AF:

0.0221

AC:

5549

AN:

251164

AF XY:

0.0202

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0397

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0165

GnomAD4 exome

AF:

0.0159

AC:

23198

AN:

1461866

Hom.:

468

Cov.:

AF XY:

0.0158

AC XY:

11454

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.124

AC:

4156

AN:

33476

American (AMR)

AF:

0.0132

AC:

589

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26136

East Asian (EAS)

AF:

0.0301

AC:

1194

AN:

39698

South Asian (SAS)

AF:

0.0242

AC:

2084

AN:

86258

European-Finnish (FIN)

AF:

0.00217

AC:

116

AN:

53420

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0123

AC:

13732

AN:

1112000

Other (OTH)

AF:

0.0199

AC:

1199

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1618

3237

4855

6474

8092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.0439

AC:

6674

AN:

152192

Hom.:

329

Cov.:

AF XY:

0.0417

AC XY:

3102

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.121

AC:

5024

AN:

41516

American (AMR)

AF:

0.0233

AC:

356

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.0384

AC:

198

AN:

5154

South Asian (SAS)

AF:

0.0282

AC:

136

AN:

4816

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0125

AC:

848

AN:

68018

Other (OTH)

AF:

0.0341

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

305

610

914

1219

1524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0229

Hom.:

500

Bravo

AF:

0.0491

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.121

AC:

534

ESP6500EA

AF:

0.0126

AC:

108

ExAC

AF:

0.0241

AC:

2930

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.39

.;.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.37

T;T;T;.

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;.;L;.

PhyloP100

2.7

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.036

D;T;T;D

Sift4G

Uncertain

0.043

D;T;D;D

Polyphen

0.041

B;.;B;B

Vest4

0.067

MPC

0.073

ClinPred

0.0055

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.12

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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