rs3914167

Variant names:

• chr5-39406395-G-C
• rs3914167
• NM_001343.4:c.-101-11974C>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.-101-11974C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,016 control chromosomes in the GnomAD database, including 39,961 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 0.72 (39961 hom., cov: 30)
• Consequence: DAB2 NM_001343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 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.-101-11974C>G		intron	N/A	NP_001334.2	P98082-1
	DAB2	NM_001244871.2		c.-101-11974C>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.-101-11974C>G		intron	N/A	ENSP00000313391.6	P98082-1
	DAB2	ENST00000908981.1		c.-101-11974C>G		intron	N/A	ENSP00000579040.1
	DAB2	ENST00000908972.1		c.-101-11974C>G		intron	N/A	ENSP00000579031.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109340 AN: 151898 Hom.: 39932 Cov.: 30

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.720 AC: 109417 AN: 152016 Hom.: 39961 Cov.: 30 AF XY: 0.715 AC XY: 53138 AN XY: 74304

African (AFR) AF: 0.797 AC: 33039 AN: 41454

American (AMR) AF: 0.622 AC: 9494 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2007 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2911 AN: 4820

European-Finnish (FIN) AF: 0.747 AC: 7889 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49220 AN: 67960

Other (OTH) AF: 0.722 AC: 1526 AN: 2114

Alfa AF: 0.727 Hom.: 5031

Bravo AF: 0.714

Asia WGS AF: 0.521 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.68
PhyloP100		0.50
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3914167;

hg19: chr5-39406497;