rs10512707

Variant names:

• chr5-39441182-A-C
• rs10512707
• ENST00000908972.1:c.-102+7394T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000511792.5(DAB2):​c.-102+20896T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 152,228 control chromosomes in the GnomAD database, including 152 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 0.019 (152 hom., cov: 32)
• Consequence: DAB2 ENST00000511792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511792.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB2	ENST00000908972.1		c.-102+7394T>G		intron	N/A	ENSP00000579031.1
	DAB2	ENST00000908971.1		c.-102+7394T>G		intron	N/A	ENSP00000579030.1
	DAB2	ENST00000511792.5	TSL:4	c.-102+20896T>G		intron	N/A	ENSP00000427541.1	D6RIA5

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2900 AN: 152110 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.00427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00468

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0191 AC: 2915 AN: 152228 Hom.: 152 Cov.: 32 AF XY: 0.0208 AC XY: 1548 AN XY: 74436

African (AFR) AF: 0.00426 AC: 177 AN: 41558

American (AMR) AF: 0.104 AC: 1581 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.0998 AC: 516 AN: 5170

South Asian (SAS) AF: 0.0391 AC: 189 AN: 4830

European-Finnish (FIN) AF: 0.00725 AC: 77 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00468 AC: 318 AN: 67992

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.0129 Hom.: 11

Bravo AF: 0.0266

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.93

Splicing

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

Other links and lift over

dbSNP: rs10512707; hg19: chr5-39441284;