Genetic Variant DAB2IP:p.Arg190Gln (chr9-121758950-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_001395010.1(DAB2IP):c.569G>A(p.Arg190Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DAB2IP
NM_001395010.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.18

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.839

BS2

High AC in GnomAdExome4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAB2IP	NM_001395010.1	MANE Select	c.569G>A	p.Arg190Gln	missense	Exon 5 of 16	NP_001381939.1	Q5VWQ8-1
DAB2IP	NM_032552.4		c.485G>A	p.Arg162Gln	missense	Exon 5 of 17	NP_115941.2	Q5VWQ8-5
DAB2IP	NM_138709.2		c.197G>A	p.Arg66Gln	missense	Exon 3 of 14	NP_619723.1	Q5VWQ8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAB2IP	ENST00000408936.8	TSL:5 MANE Select	c.569G>A	p.Arg190Gln	missense	Exon 5 of 16	ENSP00000386183.3	Q5VWQ8-1
DAB2IP	ENST00000309989.1	TSL:1	c.197G>A	p.Arg66Gln	missense	Exon 3 of 14	ENSP00000310827.1	Q5VWQ8-2
DAB2IP	ENST00000259371.7	TSL:5	c.485G>A	p.Arg162Gln	missense	Exon 5 of 17	ENSP00000259371.2	Q5VWQ8-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461446

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111932

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.49

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.47

MetaRNN

Pathogenic

0.84

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.6

PhyloP100

8.2

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Vest4

0.62

MutPred

0.38

Loss of MoRF binding (P = 0.0419)

MVP

0.98

MPC

1.7

ClinPred

1.0

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.86

Mutation Taster

=48/52

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over