Variant chr5-39377030-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DAB2	NM_001343.4 linkuse as main transcript	c.1757C>T	p.Thr586Ile	missense_variant	12/15	ENST00000320816.11	NP_001334.2	P98082-1A0A024R036B2RAW0
DAB2	NM_001244871.2 linkuse as main transcript	c.1694C>T	p.Thr565Ile	missense_variant	11/14		NP_001231800.1	P98082-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11 linkuse as main transcript	c.1757C>T	p.Thr586Ile	missense_variant	12/15	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

GnomAD3 exomes

AF:

0.0221

AC:

5549

AN:

251164

Hom.:

178

AF XY:

0.0202

AC XY:

2739

AN XY:

135738

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 SAS exome

AF:

0.0249

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

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.0301

Gnomad4 SAS exome

AF:

0.0242

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.0199

GnomAD4 genome

AF:

0.0439

AC:

6674

AN:

152192

Hom.:

329

Cov.:

AF XY:

0.0417

AC XY:

3102

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.0384

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0178

Hom.:

194

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over