9-121699325-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001395010.1(DAB2IP):c.229G>A(p.Gly77Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000179 in 1,453,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
DAB2IP
NM_001395010.1 missense, splice_region
NM_001395010.1 missense, splice_region
Scores
1
7
9
Splicing: ADA: 0.9809
1
1
Clinical Significance
Conservation
PhyloP100: 5.27
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.30744752).
BS2
High AC in GnomAdExome4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAB2IP | NM_001395010.1 | c.229G>A | p.Gly77Ser | missense_variant, splice_region_variant | 3/16 | ENST00000408936.8 | |
DAB2IP | NM_032552.4 | c.145G>A | p.Gly49Ser | missense_variant, splice_region_variant | 3/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAB2IP | ENST00000408936.8 | c.229G>A | p.Gly77Ser | missense_variant, splice_region_variant | 3/16 | 5 | NM_001395010.1 | A1 | |
DAB2IP | ENST00000259371.7 | c.145G>A | p.Gly49Ser | missense_variant, splice_region_variant | 3/17 | 5 | |||
DAB2IP | ENST00000436835.6 | c.144+20544G>A | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000135 AC: 2AN: 148514Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000572 AC: 1AN: 174976Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 99228
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GnomAD4 exome AF: 0.0000184 AC: 24AN: 1304822Hom.: 0 Cov.: 33 AF XY: 0.0000139 AC XY: 9AN XY: 648694
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GnomAD4 genome AF: 0.0000135 AC: 2AN: 148514Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 1AN XY: 72394
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.145G>A (p.G49S) alteration is located in exon 3 (coding exon 3) of the DAB2IP gene. This alteration results from a G to A substitution at nucleotide position 145, causing the glycine (G) at amino acid position 49 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Vest4
0.49, 0.50
MutPred
Gain of phosphorylation at G49 (P = 0.0252);Gain of phosphorylation at G49 (P = 0.0252);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
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Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at