chr5-39397030-T-A

Variant names:

• chr5-39397030-T-A
• rs11959928
• NM_001343.4:c.-101-2609A>T

Variant summary

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

The NM_001343.4(DAB2):​c.-101-2609A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,098 control chromosomes in the GnomAD database, including 11,802 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 0.39 (11802 hom., cov: 32)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 49 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB2	NM_001343.4	c.-101-2609A>T		intron_variant	Intron 1 of 14	ENST00000320816.11	NP_001334.2
DAB2	NM_001244871.2	c.-101-2609A>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.-101-2609A>T		intron_variant	Intron 1 of 14	1	NM_001343.4	ENSP00000313391.6

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58936 AN: 151980 Hom.: 11803 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.388 AC: 58964 AN: 152098 Hom.: 11802 Cov.: 32 AF XY: 0.386 AC XY: 28731 AN XY: 74344

African (AFR) AF: 0.313 AC: 12998 AN: 41488

American (AMR) AF: 0.414 AC: 6321 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.167 AC: 867 AN: 5184

South Asian (SAS) AF: 0.373 AC: 1796 AN: 4814

European-Finnish (FIN) AF: 0.384 AC: 4060 AN: 10580

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29760 AN: 67976

Other (OTH) AF: 0.442 AC: 931 AN: 2106

Alfa AF: 0.421 Hom.: 7664

Bravo AF: 0.387

Asia WGS AF: 0.295 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.82
PhyloP100		0.39
Mutation Taster		=99/1	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: rs11959928; hg19: chr5-39397132; COSMIC: COSV57915146; COSMIC: COSV57915146;