rs1025048

Positions:

• chr5-39429414-C-A
• chr5-39429414-C-G
• chr5-39429414-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000511792.5(DAB2):​c.-102+32664G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 151,996 control chromosomes in the GnomAD database, including 6 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 0.0050 (6 hom., cov: 32)
• Consequence: DAB2 ENST00000511792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAd4 at 759 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000511792.5	c.-102+32664G>T		intron_variant		4		ENSP00000427541
DAB2	ENST00000509457.1	n.78-11069G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00500 AC: 759 AN: 151880 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000569

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00558

Gnomad OTH AF: 0.0101

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

GnomAD4 genome AF: 0.00499 AC: 759 AN: 151996 Hom.: 6 Cov.: 32 AF XY: 0.00507 AC XY: 377 AN XY: 74288

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.000569

Gnomad4 NFE AF: 0.00558

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.000408 Hom.: 330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1025048; hg19: chr5-39429516;