dbSNP rs763394734: DAB2IP:p.Pro72Arg (chr9-121678768-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395010.1(DAB2IP):c.215C>G(p.Pro72Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,396 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DAB2IP
NM_001395010.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.62

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB2IP	NM_001395010.1 link	c.215C>G	p.Pro72Arg	missense_variant	Exon 2 of 16	ENST00000408936.8	NP_001381939.1
DAB2IP	NM_032552.4 link	c.131C>G	p.Pro44Arg	missense_variant	Exon 2 of 17		NP_115941.2	Q5VWQ8-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB2IP	ENST00000408936.8 link	c.215C>G	p.Pro72Arg	missense_variant	Exon 2 of 16	5	NM_001395010.1	ENSP00000386183.3		Q5VWQ8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441396

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

.;.;.;D

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.8

.;.;.;M

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.6

D;D;.;D

REVEL

Benign

0.21

Sift

Benign

0.041

D;D;.;D

Sift4G

Pathogenic

0.0

D;T;.;D

Vest4

0.54, 0.54

MutPred

0.36

Gain of methylation at P44 (P = 0.0113);Gain of methylation at P44 (P = 0.0113);.;.;

MVP

0.67

MPC

1.6

ClinPred

0.98

GERP RS

4.7

Varity_R

0.20

gMVP

0.57

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over