Variant 5-39382671-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001343.4(DAB2):c.1288A>G(p.Ile430Val) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,614,034 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

DAB2
NM_001343.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008519262).

BP6

Variant 5-39382671-T-C is Benign according to our data. Variant chr5-39382671-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 718436.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB2	NM_001343.4 linkuse as main transcript	c.1288A>G	p.Ile430Val	missense_variant	10/15	ENST00000320816.11
DAB2	NM_001244871.2 linkuse as main transcript	c.1225A>G	p.Ile409Val	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB2	ENST00000320816.11 linkuse as main transcript	c.1288A>G	p.Ile430Val	missense_variant	10/15	1	NM_001343.4	P3	P98082-1
DAB2	ENST00000509337.5 linkuse as main transcript	c.1225A>G	p.Ile409Val	missense_variant	8/13	1		A1	P98082-3
DAB2	ENST00000545653.5 linkuse as main transcript	c.1225A>G	p.Ile409Val	missense_variant	9/14	5		A1	P98082-3
DAB2	ENST00000339788.10 linkuse as main transcript	c.688-1055A>G		intron_variant		5			P98082-2

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00144

AC:

361

AN:

251028

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00481

Gnomad NFE exome

AF:

0.00188

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00128

AC:

1872

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

910

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00464

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152192

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000933

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00158

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-0.60

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.29

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.57

MVP

0.57

MPC

0.37

ClinPred

0.075

GERP RS

5.6

Varity_R

0.13

gMVP

0.27

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over