5-39377204-G-A

Position:

chr5-39377204-G-A

Variant summary

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

The NM_001343.4(DAB2):c.1583C>T(p.Ala528Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 1 hom. )

Consequence

DAB2
NM_001343.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47

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=0.021187156).

BP6

Variant 5-39377204-G-A is Benign according to our data. Variant chr5-39377204-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2407271.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB2	NM_001343.4 linkuse as main transcript	c.1583C>T	p.Ala528Val	missense_variant	12/15	ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2 linkuse as main transcript	c.1520C>T	p.Ala507Val	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.1583C>T	p.Ala528Val	missense_variant	12/15	1	NM_001343.4	ENSP00000313391	P3	P98082-1
DAB2	ENST00000509337.5 linkuse as main transcript	c.1520C>T	p.Ala507Val	missense_variant	10/13	1		ENSP00000426245	A1	P98082-3
DAB2	ENST00000545653.5 linkuse as main transcript	c.1520C>T	p.Ala507Val	missense_variant	11/14	5		ENSP00000439919	A1	P98082-3
DAB2	ENST00000339788.10 linkuse as main transcript	c.929C>T	p.Ala310Val	missense_variant	11/14	5		ENSP00000345508		P98082-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250474

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000125

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.0

DANN

Benign

0.51

DEOGEN2

Benign

0.26

.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.46

T;T;T;.

M_CAP

Benign

0.0023

MetaRNN

Benign

0.021

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.2

.;.;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.63

N;N;N;N

REVEL

Benign

0.056

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.79

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.077

MVP

0.19

MPC

0.065

ClinPred

0.0093

GERP RS

-0.061

Varity_R

0.022

gMVP

0.12

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