rs3747851

chr9-121758981-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001395010.1(DAB2IP):c.600G>A(p.Ala200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,612,336 control chromosomes in the GnomAD database, including 1,154 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (92 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1062 hom.)
• Consequence: DAB2IP NM_001395010.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.43

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-4.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB2IP	NM_001395010.1	c.600G>A	p.Ala200=	synonymous_variant	5/16	ENST00000408936.8
DAB2IP	NM_032552.4	c.516G>A	p.Ala172=	synonymous_variant	5/17
DAB2IP	NM_138709.2	c.228G>A	p.Ala76=	synonymous_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB2IP	ENST00000408936.8	c.600G>A	p.Ala200=	synonymous_variant	5/16	5	NM_001395010.1	A1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1753 AN: 152136 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.0282 AC: 6976 AN: 247104 Hom.: 351 AF XY: 0.0262 AC XY: 3496 AN XY: 133318

Gnomad AFR exome AF: 0.00171

Gnomad AMR exome AF: 0.0754

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.155

Gnomad SAS exome AF: 0.0319

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0109 AC: 15859 AN: 1460082 Hom.: 1062 Cov.: 31 AF XY: 0.0112 AC XY: 8141 AN XY: 726032

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.0694

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.0321

Gnomad4 FIN exome AF: 0.0201

Gnomad4 NFE exome AF: 0.000423

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0115 AC: 1753 AN: 152254 Hom.: 92 Cov.: 33 AF XY: 0.0134 AC XY: 1000 AN XY: 74428

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00429 Hom.: 33

Bravo AF: 0.0133

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.13
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs3747851; hg19: chr9-124521260; COSMIC: COSV52260158; COSMIC: COSV52260158;