9-121592547-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032552.4(DAB2IP):c.40+25319T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,090 control chromosomes in the GnomAD database, including 6,057 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 0.27 (6057 hom., cov: 32)
• Consequence: DAB2IP NM_032552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB2IP	NM_032552.4	c.40+25319T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB2IP	ENST00000259371.7	c.40+25319T>C		intron_variant		5
DAB2IP	ENST00000436835.6	c.40+25319T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41069 AN: 151970 Hom.: 6053 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 41095 AN: 152090 Hom.: 6057 Cov.: 32 AF XY: 0.261 AC XY: 19436 AN XY: 74358

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.291

Alfa AF: 0.309 Hom.: 7710

Bravo AF: 0.271

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.56

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: rs10513376; hg19: chr9-124354826; COSMIC: COSV52256422;