rs835223

Variant names:

• chr5-39381255-C-T
• rs835223
• NM_001343.4:c.1504+199G>A

Variant summary

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

The NM_001343.4(DAB2):​c.1504+199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,882 control chromosomes in the GnomAD database, including 10,282 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 0.36 (10282 hom., cov: 31)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 11 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=-0.89).
• 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 rank	MANE	Protein	UniProt
DAB2	NM_001343.4	c.1504+199G>A		intron_variant	Intron 11 of 14	ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2	c.1441+199G>A		intron_variant	Intron 10 of 13		NP_001231800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB2	ENST00000320816.11	c.1504+199G>A		intron_variant	Intron 11 of 14	1	NM_001343.4	ENSP00000313391.6

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54002 AN: 151764 Hom.: 10286 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.356 AC: 54008 AN: 151882 Hom.: 10282 Cov.: 31 AF XY: 0.356 AC XY: 26405 AN XY: 74246

African (AFR) AF: 0.241 AC: 9982 AN: 41398

American (AMR) AF: 0.400 AC: 6109 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1636 AN: 3470

East Asian (EAS) AF: 0.0624 AC: 321 AN: 5146

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4810

European-Finnish (FIN) AF: 0.380 AC: 4007 AN: 10538

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28815 AN: 67942

Other (OTH) AF: 0.417 AC: 879 AN: 2110

Alfa AF: 0.404 Hom.: 6960

Bravo AF: 0.351

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.45
PhyloP100		-1.2
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: rs835223; hg19: chr5-39381357;