rs2255280

Positions:

• chr5-39394887-C-A
• chr5-39394887-C-G
• chr5-39394887-C-T

Variant summary

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

The NM_001343.4(DAB2):​c.-101-466G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 152,306 control chromosomes in the GnomAD database, including 72,867 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 0.98 (72867 hom., cov: 32)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB2	NM_001343.4	c.-101-466G>T		intron_variant		ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2	c.-101-466G>T		intron_variant			NP_001231800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11	c.-101-466G>T		intron_variant		1	NM_001343.4	ENSP00000313391.6

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148464 AN: 152188 Hom.: 72817 Cov.: 32

Gnomad AFR AF: 0.995

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.980

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

GnomAD4 genome AF: 0.975 AC: 148574 AN: 152306 Hom.: 72867 Cov.: 32 AF XY: 0.973 AC XY: 72462 AN XY: 74476

Gnomad4 AFR AF: 0.996

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.990

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.979

Alfa AF: 0.986 Hom.: 77985

Bravo AF: 0.969

Asia WGS AF: 0.826 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.49

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: rs2255280; hg19: chr5-39394989;