9-121757153-A-G

Variant names:

• chr9-121757153-A-G
• NM_001395010.1:c.503A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001395010.1(DAB2IP):​c.503A>G​(p.Asp168Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DAB2IP NM_001395010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

DAB2IP (HGNC:17294): (DAB2 interacting protein) DAB2IP is a Ras (MIM 190020) GTPase-activating protein (GAP) that acts as a tumor suppressor. The DAB2IP gene is inactivated by methylation in prostate and breast cancers (Yano et al., 2005 [PubMed 15386433]).[supplied by OMIM, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB2IP	NM_001395010.1	c.503A>G	p.Asp168Gly	missense_variant	Exon 4 of 16	ENST00000408936.8	NP_001381939.1
DAB2IP	NM_032552.4	c.419A>G	p.Asp140Gly	missense_variant	Exon 4 of 17		NP_115941.2
DAB2IP	NM_138709.2	c.131A>G	p.Asp44Gly	missense_variant	Exon 2 of 14		NP_619723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB2IP	ENST00000408936.8	c.503A>G	p.Asp168Gly	missense_variant	Exon 4 of 16	5	NM_001395010.1	ENSP00000386183.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.419A>G (p.D140G) alteration is located in exon 4 (coding exon 4) of the DAB2IP gene. This alteration results from a A to G substitution at nucleotide position 419, causing the aspartic acid (D) at amino acid position 140 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	.;T;.;D;.;.;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	1.4	.;.;.;L;.;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.4	D;D;D;D;D;.;D;.
REVEL	Pathogenic	0.91
Sift	Benign	0.035	D;D;D;D;D;.;D;.
Sift4G	Uncertain	0.0030	D;D;D;D;D;.;D;.
Vest4		0.86, 0.94, 0.83
MutPred		0.47		Loss of loop (P = 0.0374);.;Loss of loop (P = 0.0374);.;.;.;.;.;
MVP		0.97
MPC		1.3
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.62
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-124519432;