9-121678745-C-A

Variant names:

• chr9-121678745-C-A
• NM_001395010.1:c.192C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395010.1(DAB2IP):​c.192C>A​(p.Ser64Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAB2IP NM_001395010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2852859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395010.1. 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
	DAB2IP	NM_001395010.1	MANE Select	c.192C>A	p.Ser64Arg	missense	Exon 2 of 16	NP_001381939.1	Q5VWQ8-1
	DAB2IP	NM_032552.4		c.108C>A	p.Ser36Arg	missense	Exon 2 of 17	NP_115941.2	Q5VWQ8-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB2IP	ENST00000408936.8	TSL:5 MANE Select	c.192C>A	p.Ser64Arg	missense	Exon 2 of 16	ENSP00000386183.3	Q5VWQ8-1
	DAB2IP	ENST00000259371.7	TSL:5	c.108C>A	p.Ser36Arg	missense	Exon 2 of 17	ENSP00000259371.2	Q5VWQ8-5
	DAB2IP	ENST00000489314.1	TSL:3	c.171C>A	p.Ser57Arg	missense	Exon 2 of 2	ENSP00000497730.1	A0A3B3ITC7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447816 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718870

African (AFR) AF: 0.00 AC: 0 AN: 32946

American (AMR) AF: 0.00 AC: 0 AN: 43640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 38774

South Asian (SAS) AF: 0.00 AC: 0 AN: 84440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104580

Other (OTH) AF: 0.00 AC: 0 AN: 59662

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	0.00035	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Benign	0.036	D
Sift4G	Uncertain	0.037	D
Vest4		0.39
MutPred		0.16		Loss of phosphorylation at S36 (P = 0.0035)
MVP		0.69
MPC		0.82
ClinPred		0.79	D
GERP RS		4.7
Varity_R		0.24
gMVP		0.51
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr9-124441024;