9-121678705-G-T

Variant names:

• chr9-121678705-G-T
• rs377424901
• NM_001395010.1:c.152G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001395010.1(DAB2IP):​c.152G>T​(p.Arg51Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000265 in 1,587,852 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. R51Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: DAB2IP NM_001395010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0973244).
• BS2: High AC in GnomAd4 at 29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB2IP	NM_001395010.1	MANE Select	c.152G>T	p.Arg51Leu	missense	Exon 2 of 16	NP_001381939.1	Q5VWQ8-1
	DAB2IP	NM_032552.4		c.68G>T	p.Arg23Leu	missense	Exon 2 of 17	NP_115941.2	Q5VWQ8-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB2IP	ENST00000408936.8	TSL:5 MANE Select	c.152G>T	p.Arg51Leu	missense	Exon 2 of 16	ENSP00000386183.3	Q5VWQ8-1
	DAB2IP	ENST00000259371.7	TSL:5	c.68G>T	p.Arg23Leu	missense	Exon 2 of 17	ENSP00000259371.2	Q5VWQ8-5
	DAB2IP	ENST00000489314.1	TSL:3	c.131G>T	p.Arg44Leu	missense	Exon 2 of 2	ENSP00000497730.1	A0A3B3ITC7

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000367 AC: 8 AN: 217852 AF XY: 0.0000420

Gnomad AFR exome AF: 0.000559

Gnomad AMR exome AF: 0.0000322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000906 AC: 13 AN: 1435538 Hom.: 0 Cov.: 30 AF XY: 0.00000984 AC XY: 7 AN XY: 711404

African (AFR) AF: 0.000307 AC: 10 AN: 32522

American (AMR) AF: 0.0000235 AC: 1 AN: 42474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 37886

South Asian (SAS) AF: 0.00 AC: 0 AN: 82622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097648

Other (OTH) AF: 0.0000338 AC: 2 AN: 59148

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74476

African (AFR) AF: 0.000625 AC: 26 AN: 41568

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.20
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Vest4		0.70
MVP		0.81
MPC		1.7
ClinPred		0.19	T
GERP RS		4.7
Varity_R		0.27
gMVP		0.59
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377424901; hg19: chr9-124440984;