Genetic Variant DAB2IP:p.Ala113Val (chr9-121699434-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395010.1(DAB2IP):c.338C>T(p.Ala113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,172 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 (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

DAB2IP
NM_001395010.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20437998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB2IP	NM_001395010.1 link	c.338C>T	p.Ala113Val	missense_variant	Exon 3 of 16	ENST00000408936.8	NP_001381939.1
DAB2IP	NM_032552.4 link	c.254C>T	p.Ala85Val	missense_variant	Exon 3 of 17		NP_115941.2	Q5VWQ8-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DAB2IP	ENST00000408936.8 link	c.338C>T	p.Ala113Val	missense_variant	Exon 3 of 16	5	NM_001395010.1	ENSP00000386183.3	Q5VWQ8-1
DAB2IP	ENST00000259371.7 link	c.254C>T	p.Ala85Val	missense_variant	Exon 3 of 17	5		ENSP00000259371.2	Q5VWQ8-5
DAB2IP	ENST00000436835.6 link	n.144+20653C>T		intron_variant	Intron 2 of 5	3		ENSP00000409327.2	F6R503

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000683

AC:

AN:

146374

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000473

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1296058

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

642424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.80e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150114

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73248

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000886

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.254C>T (p.A85V) alteration is located in exon 3 (coding exon 3) of the DAB2IP gene. This alteration results from a C to T substitution at nucleotide position 254, causing the alanine (A) at amino acid position 85 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

.;.;T;.

Eigen

Benign

0.0031

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;.;L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.27

N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Vest4

0.32, 0.29

MutPred

0.38

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);.;.;

MVP

0.31

MPC

0.60

ClinPred

0.26

GERP RS

2.5

Varity_R

0.079

gMVP

0.44

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