rs700242

Variant names:

• chr5-39384786-A-C
• rs700242
• NM_001343.4:c.688-1515T>G

Variant summary

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

The NM_001343.4(DAB2):​c.688-1515T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,606 control chromosomes in the GnomAD database, including 10,586 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 (10586 hom., cov: 30)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 9 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]

ENSG00000289699 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001343.4. 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
	DAB2	NM_001343.4	MANE Select	c.688-1515T>G		intron	N/A	NP_001334.2	P98082-1
	DAB2	NM_001244871.2		c.625-1515T>G		intron	N/A	NP_001231800.1	P98082-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB2	ENST00000320816.11	TSL:1 MANE Select	c.688-1515T>G		intron	N/A	ENSP00000313391.6	P98082-1
	DAB2	ENST00000509337.5	TSL:1	c.625-1515T>G		intron	N/A	ENSP00000426245.1	P98082-3
	DAB2	ENST00000908981.1		c.706-1515T>G		intron	N/A	ENSP00000579040.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55358 AN: 151484 Hom.: 10591 Cov.: 30

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.365 AC: 55381 AN: 151606 Hom.: 10586 Cov.: 30 AF XY: 0.366 AC XY: 27103 AN XY: 74046

African (AFR) AF: 0.264 AC: 10904 AN: 41318

American (AMR) AF: 0.407 AC: 6193 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1733 AN: 3458

East Asian (EAS) AF: 0.133 AC: 686 AN: 5150

South Asian (SAS) AF: 0.365 AC: 1752 AN: 4802

European-Finnish (FIN) AF: 0.378 AC: 3959 AN: 10476

Middle Eastern (MID) AF: 0.486 AC: 141 AN: 290

European-Non Finnish (NFE) AF: 0.423 AC: 28724 AN: 67878

Other (OTH) AF: 0.425 AC: 894 AN: 2106

Alfa AF: 0.391 Hom.: 1982

Bravo AF: 0.362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.77
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs700242; hg19: chr5-39384888;