Variant chr9-121678705-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395010.1(DAB2IP):c.152G>T(p.Arg51Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000265 in 1,587,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R51Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

DAB2IP
NM_001395010.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90

Variant links:

Genes affected

DAB2IP (HGNC:17294): (DAB2 interacting protein) DAB2IP is a Ras (MIM 190020) GTPase-activating protein (GAP) that acts as a tumor suppressor. The DAB2IP gene is inactivated by methylation in prostate and breast cancers (Yano et al., 2005 [PubMed 15386433]).[supplied by OMIM, May 2010]

DAB2IP 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=0.0973244).

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB2IP	NM_001395010.1 linkuse as main transcript	c.152G>T	p.Arg51Leu	missense_variant	2/16	ENST00000408936.8
DAB2IP	NM_032552.4 linkuse as main transcript	c.68G>T	p.Arg23Leu	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB2IP	ENST00000408936.8 linkuse as main transcript	c.152G>T	p.Arg51Leu	missense_variant	2/16	5	NM_001395010.1	A1	Q5VWQ8-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000956

GnomAD3 exomes

AF:

0.0000367

AC:

AN:

217852

Hom.:

AF XY:

0.0000420

AC XY:

AN XY:

119016

show subpopulations

Gnomad AFR exome

AF:

0.000559

Gnomad AMR exome

AF:

0.0000322

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:

0.00000906

AC:

AN:

1435538

Hom.:

Cov.:

AF XY:

0.00000984

AC XY:

AN XY:

711404

show subpopulations

Gnomad4 AFR exome

AF:

0.000307

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.000190

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.0000653

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:

0.000946

Bravo

AF:

0.000181

ExAC

AF:

0.0000248

AC:

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

May 06, 2022

The c.68G>T (p.R23L) alteration is located in exon 2 (coding exon 2) of the DAB2IP gene. This alteration results from a G to T substitution at nucleotide position 68, causing the arginine (R) at amino acid position 23 to be replaced by a leucine (L). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.0072

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.097

T;T;T;T

MetaSVM

Benign

-0.64

MutationTaster

Benign

0.54

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.2

D;D;.;D

REVEL

Benign

0.20

Sift

Benign

0.11

T;T;.;T

Sift4G

Benign

0.12

T;T;.;T

Vest4

0.70, 0.70

MVP

0.81

MPC

1.7

ClinPred

0.19

GERP RS

4.7

Varity_R

0.27

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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