5-39376785-C-T

Position:

chr5-39376785-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001343.4(DAB2):c.2002G>A(p.Ala668Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

DAB2
NM_001343.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08011815).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB2	NM_001343.4 linkuse as main transcript	c.2002G>A	p.Ala668Thr	missense_variant	12/15	ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2 linkuse as main transcript	c.1939G>A	p.Ala647Thr	missense_variant	11/14		NP_001231800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11 linkuse as main transcript	c.2002G>A	p.Ala668Thr	missense_variant	12/15	1	NM_001343.4	ENSP00000313391	P3	P98082-1
DAB2	ENST00000509337.5 linkuse as main transcript	c.1939G>A	p.Ala647Thr	missense_variant	10/13	1		ENSP00000426245	A1	P98082-3
DAB2	ENST00000545653.5 linkuse as main transcript	c.1939G>A	p.Ala647Thr	missense_variant	11/14	5		ENSP00000439919	A1	P98082-3
DAB2	ENST00000339788.10 linkuse as main transcript	c.1348G>A	p.Ala450Thr	missense_variant	11/14	5		ENSP00000345508		P98082-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000247

AC:

AN:

250958

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000794

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000148

AC:

216

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

104

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000158

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.000340

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.2002G>A (p.A668T) alteration is located in exon 12 (coding exon 11) of the DAB2 gene. This alteration results from a G to A substitution at nucleotide position 2002, causing the alanine (A) at amino acid position 668 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

.;.;T;.

Eigen

Benign

0.079

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D;D;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.080

T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.9

.;.;M;.

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

0.98

D;.;D;D

Vest4

0.48

MVP

0.54

MPC

0.24

ClinPred

0.36

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.35

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