chr9-121678773-C-T

Variant names:

• chr9-121678773-C-T
• rs759693049
• NM_001395010.1:c.220C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001395010.1(DAB2IP):​c.220C>T​(p.Arg74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,590,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: DAB2IP NM_001395010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35354948).
• BS2: High AC in GnomAdExome4 at 27 AD gene.

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.220C>T	p.Arg74Trp	missense	Exon 2 of 16	NP_001381939.1	Q5VWQ8-1
	DAB2IP	NM_032552.4		c.136C>T	p.Arg46Trp	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.220C>T	p.Arg74Trp	missense	Exon 2 of 16	ENSP00000386183.3	Q5VWQ8-1
	DAB2IP	ENST00000259371.7	TSL:5	c.136C>T	p.Arg46Trp	missense	Exon 2 of 17	ENSP00000259371.2	Q5VWQ8-5
	DAB2IP	ENST00000489314.1	TSL:3	c.199C>T	p.Arg67Trp	missense	Exon 2 of 2	ENSP00000497730.1	A0A3B3ITC7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 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: 0.000193

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: 0.0000409 AC: 9 AN: 219802 AF XY: 0.0000496

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000201

Gnomad OTH exome AF: 0.000190

GnomAD4 exome AF: 0.0000188 AC: 27 AN: 1438644 Hom.: 0 Cov.: 30 AF XY: 0.0000168 AC XY: 12 AN XY: 713874

African (AFR) AF: 0.0000306 AC: 1 AN: 32632

American (AMR) AF: 0.000140 AC: 6 AN: 43010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38196

South Asian (SAS) AF: 0.0000598 AC: 5 AN: 83578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1099944

Other (OTH) AF: 0.0000169 AC: 1 AN: 59284

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000381 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000331 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.85
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.74
MVP		0.39
MPC		1.5
ClinPred		0.69	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.55
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs759693049; hg19: chr9-124441052; COSMIC: COSV52253995;