rs3849765

Variant names:

• chr5-39412696-G-A
• rs3849765
• NM_001343.4:c.-102+12108C>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+12108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,188 control chromosomes in the GnomAD database, including 68,750 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 0.95 (68750 hom., cov: 30)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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]

ENSG00000289699 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB2	NM_001343.4	c.-102+12108C>T		intron_variant	Intron 1 of 14	ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2	c.-102+12108C>T		intron_variant	Intron 1 of 13		NP_001231800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11	c.-102+12108C>T		intron_variant	Intron 1 of 14	1	NM_001343.4	ENSP00000313391.6

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144147 AN: 152070 Hom.: 68698 Cov.: 30

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.948 AC: 144258 AN: 152188 Hom.: 68750 Cov.: 30 AF XY: 0.945 AC XY: 70282 AN XY: 74398

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.960

Gnomad4 NFE AF: 0.959

Gnomad4 OTH AF: 0.959

Alfa AF: 0.956 Hom.: 8654

Bravo AF: 0.947

Asia WGS AF: 0.784 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
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: rs3849765; hg19: chr5-39412798;