9-121678773-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001395010.1(DAB2IP):​c.220C>T​(p.Arg74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,590,982 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. R74L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DAB2IP
NM_001395010.1 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.35354948).
BS2
High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DAB2IPNM_001395010.1 linkc.220C>T p.Arg74Trp missense_variant Exon 2 of 16 ENST00000408936.8 NP_001381939.1
DAB2IPNM_032552.4 linkc.136C>T p.Arg46Trp missense_variant Exon 2 of 17 NP_115941.2 Q5VWQ8-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DAB2IPENST00000408936.8 linkc.220C>T p.Arg74Trp missense_variant Exon 2 of 16 5 NM_001395010.1 ENSP00000386183.3 Q5VWQ8-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152220
Hom.:
0
Cov.:
32
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:
0.000193
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:
0.0000409
AC:
9
AN:
219802
Hom.:
0
AF XY:
0.0000496
AC XY:
6
AN XY:
120978
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000159
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000362
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000201
Gnomad OTH exome
AF:
0.000190
GnomAD4 exome
AF:
0.0000188
AC:
27
AN:
1438644
Hom.:
0
Cov.:
30
AF XY:
0.0000168
AC XY:
12
AN XY:
713874
show subpopulations
Gnomad4 AFR exome
AF:
0.0000306
Gnomad4 AMR exome
AF:
0.000140
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000262
Gnomad4 SAS exome
AF:
0.0000598
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000118
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152338
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000510
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000331
AC:
4
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.136C>T (p.R46W) alteration is located in exon 2 (coding exon 2) of the DAB2IP gene. This alteration results from a C to T substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a tryptophan (W). 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
Pathogenic
0.85
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
.;.;.;D
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.35
T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.0
.;.;.;M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-4.9
D;D;.;D
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D;D;.;D
Sift4G
Pathogenic
0.0010
D;D;.;D
Vest4
0.74, 0.77
MVP
0.39
MPC
1.5
ClinPred
0.69
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.37
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs759693049; hg19: chr9-124441052; COSMIC: COSV52253995; API