rs11951093

chr5-39421634-G-Achr5-39421634-G-T

Variant summary

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

The NM_001343.4(DAB2):c.-102+3170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,054 control chromosomes in the GnomAD database, including 10,599 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 0.37 (10599 hom., cov: 31)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB2	NM_001343.4	c.-102+3170C>T		intron_variant		ENST00000320816.11
DAB2	NM_001244871.2	c.-102+3170C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB2	ENST00000320816.11	c.-102+3170C>T		intron_variant		1	NM_001343.4	P3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55584 AN: 151936 Hom.: 10604 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.366 AC: 55596 AN: 152054 Hom.: 10599 Cov.: 31 AF XY: 0.366 AC XY: 27188 AN XY: 74346

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.433

Alfa AF: 0.342 Hom.: 1703

Bravo AF: 0.363

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.9
Dann	Benign	0.38

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: rs11951093; hg19: chr5-39421736;