Genetic Variant DAB2IP:p.Arg198Trp (chr9-121758973-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001395010.1(DAB2IP):c.592C>T(p.Arg198Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,460,796 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: 0.000019 ( 0 hom. )

Consequence

DAB2IP
NM_001395010.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

BS2

High AC in GnomAdExome4 at 28 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.592C>T	p.Arg198Trp	missense	Exon 5 of 16	NP_001381939.1	Q5VWQ8-1
DAB2IP	NM_032552.4		c.508C>T	p.Arg170Trp	missense	Exon 5 of 17	NP_115941.2	Q5VWQ8-5
DAB2IP	NM_138709.2		c.220C>T	p.Arg74Trp	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.592C>T	p.Arg198Trp	missense	Exon 5 of 16	ENSP00000386183.3	Q5VWQ8-1
DAB2IP	ENST00000309989.1	TSL:1	c.220C>T	p.Arg74Trp	missense	Exon 3 of 14	ENSP00000310827.1	Q5VWQ8-2
DAB2IP	ENST00000259371.7	TSL:5	c.508C>T	p.Arg170Trp	missense	Exon 5 of 17	ENSP00000259371.2	Q5VWQ8-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

248750

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460796

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000448

AC:

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.000101

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111786

Other (OTH)

AF:

0.0000331

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.00000756

ExAC

AF:

0.0000412

AC:

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

0.77

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.85

MetaSVM

Pathogenic

0.80

MutationAssessor

Uncertain

2.1

PhyloP100

2.6

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.2

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Vest4

0.90

MutPred

0.45

Loss of disorder (P = 0.0116)

MVP

0.95

MPC

1.6

ClinPred

0.97

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.89

Mutation Taster

=16/84

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