rs3822460

Positions:

• chr5-39386242-T-C

Variant summary

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

The NM_001343.4(DAB2):​c.687+2063A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,280 control chromosomes in the GnomAD database, including 763 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 0.060 (763 hom., cov: 32)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

Genes affected

DAB2 (HGNC:2662): (DAB adaptor protein 2) This gene encodes a mitogen-responsive phosphoprotein. It is expressed in normal ovarian epithelial cells, but is down-regulated or absent from ovarian carcinoma cell lines, suggesting its role as a tumor suppressor. This protein binds to the SH3 domains of GRB2, an adaptor protein that couples tyrosine kinase receptors to SOS (a guanine nucleotide exchange factor for Ras), via its C-terminal proline-rich sequences, and may thus modulate growth factor/Ras pathways by competing with SOS for binding to GRB2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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 (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB2	NM_001343.4	c.687+2063A>G		intron_variant		ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2	c.624+2557A>G		intron_variant			NP_001231800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11	c.687+2063A>G		intron_variant		1	NM_001343.4	ENSP00000313391	P3

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9145 AN: 152162 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0601 AC: 9159 AN: 152280 Hom.: 763 Cov.: 32 AF XY: 0.0602 AC XY: 4487 AN XY: 74474

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0314 Hom.: 82

Bravo AF: 0.0662

Asia WGS AF: 0.126 AC: 438 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	4.4
DANN	Benign	0.48

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: rs3822460; hg19: chr5-39386344;