9-121699437-C-T

Variant names:

• chr9-121699437-C-T
• rs1363376652
• NM_001395010.1:c.341C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395010.1(DAB2IP):​c.341C>T​(p.Ala114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 1,297,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAB2IP NM_001395010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.336
• 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]

ENSG00000293923 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19925645).

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.341C>T	p.Ala114Val	missense	Exon 3 of 16	NP_001381939.1	Q5VWQ8-1
	DAB2IP	NM_032552.4		c.257C>T	p.Ala86Val	missense	Exon 3 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.341C>T	p.Ala114Val	missense	Exon 3 of 16	ENSP00000386183.3	Q5VWQ8-1
	DAB2IP	ENST00000259371.7	TSL:5	c.257C>T	p.Ala86Val	missense	Exon 3 of 17	ENSP00000259371.2	Q5VWQ8-5
	DAB2IP	ENST00000436835.6	TSL:3	n.144+20656C>T		intron	N/A	ENSP00000409327.2	F6R503

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000681 AC: 1 AN: 146750 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000465

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000231 AC: 3 AN: 1297130 Hom.: 0 Cov.: 33 AF XY: 0.00000156 AC XY: 1 AN XY: 642982

African (AFR) AF: 0.00 AC: 0 AN: 26504

American (AMR) AF: 0.0000970 AC: 3 AN: 30938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20774

East Asian (EAS) AF: 0.00 AC: 0 AN: 26868

South Asian (SAS) AF: 0.00 AC: 0 AN: 69210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021244

Other (OTH) AF: 0.00 AC: 0 AN: 50840

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73312

African (AFR) AF: 0.00 AC: 0 AN: 41208

American (AMR) AF: 0.00 AC: 0 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67294

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.34
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.087
Sift	Benign	0.29	T
Sift4G	Benign	0.52	T
Vest4		0.32
MutPred		0.34		Loss of helix (P = 0.0167)
MVP		0.44
MPC		0.57
ClinPred		0.24	T
GERP RS		2.5
Varity_R		0.064
gMVP		0.46
Mutation Taster		=93/7	polymorphism

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: rs1363376652; hg19: chr9-124461716;