9-121699434-C-G

Variant names:

• chr9-121699434-C-G
• rs767176388
• NM_001395010.1:c.338C>G

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.338C>G​(p.Ala113Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,296,062 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: DAB2IP NM_001395010.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• 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=0.1776301).

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.338C>G	p.Ala113Gly	missense	Exon 3 of 16	NP_001381939.1	Q5VWQ8-1
	DAB2IP	NM_032552.4		c.254C>G	p.Ala85Gly	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.338C>G	p.Ala113Gly	missense	Exon 3 of 16	ENSP00000386183.3	Q5VWQ8-1
	DAB2IP	ENST00000259371.7	TSL:5	c.254C>G	p.Ala85Gly	missense	Exon 3 of 17	ENSP00000259371.2	Q5VWQ8-5
	DAB2IP	ENST00000436835.6	TSL:3	n.144+20653C>G		intron	N/A	ENSP00000409327.2	F6R503

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1296062 Hom.: 0 Cov.: 33 AF XY: 0.00000156 AC XY: 1 AN XY: 642428

African (AFR) AF: 0.00 AC: 0 AN: 26478

American (AMR) AF: 0.00 AC: 0 AN: 30880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20754

East Asian (EAS) AF: 0.00 AC: 0 AN: 26824

South Asian (SAS) AF: 0.00 AC: 0 AN: 69108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5102

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1020606

Other (OTH) AF: 0.00 AC: 0 AN: 50766

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.078
Sift	Benign	0.86	T
Sift4G	Benign	0.24	T
Vest4		0.24
MutPred		0.38		Loss of helix (P = 0.0041)
MVP		0.37
MPC		0.62
ClinPred		0.34	T
GERP RS		2.5
Varity_R		0.079
gMVP		0.36
Mutation Taster		=85/15	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: rs767176388; hg19: chr9-124461713;