Variant chr5-39377273-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001343.4(DAB2):c.1514C>T(p.Thr505Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00151 in 1,609,264 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

DAB2
NM_001343.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.65

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004726529).

BP6

Variant 5-39377273-G-A is Benign according to our data. Variant chr5-39377273-G-A is described in ClinVar as [Benign]. Clinvar id is 782450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 204 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB2	NM_001343.4 link	c.1514C>T	p.Thr505Ile	missense_variant	12/15	ENST00000320816.11	NP_001334.2	P98082-1A0A024R036B2RAW0
DAB2	NM_001244871.2 link	c.1451C>T	p.Thr484Ile	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 link	c.1514C>T	p.Thr505Ile	missense_variant	12/15	1	NM_001343.4	ENSP00000313391.6		P98082-1

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00188

AC:

462

AN:

246230

Hom.:

AF XY:

0.00185

AC XY:

246

AN XY:

133008

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.000236

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0141

Gnomad SAS exome

AF:

0.000570

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00152

GnomAD4 exome

AF:

0.00153

AC:

2229

AN:

1456986

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1070

AN XY:

724184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000318

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0150

Gnomad4 SAS exome

AF:

0.000748

Gnomad4 FIN exome

AF:

0.000694

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00134

AC:

204

AN:

152278

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0129

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00175

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00195

AC:

237

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Uncertain

0.45

.;.;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.34

T;T;T;.

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.036

D;T;T;D

Sift4G

Benign

0.082

T;T;T;T

Polyphen

0.041

B;.;B;B

Vest4

0.12

MVP

0.31

MPC

0.070

ClinPred

0.029

GERP RS

5.5

Varity_R

0.10

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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