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GeneBe

9-121758976-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4BP6_ModerateBP7BS1BS2

The NM_001395010.1(DAB2IP):c.595C>A(p.Arg199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,612,870 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 14 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 14 hom. )

Consequence

DAB2IP
NM_001395010.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.15).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-121758976-C-A is Benign according to our data. Variant chr9-121758976-C-A is described in ClinVar as [Benign]. Clinvar id is 713727.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.92 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00856 (1304/152286) while in subpopulation AFR AF= 0.0256 (1063/41556). AF 95% confidence interval is 0.0243. There are 14 homozygotes in gnomad4. There are 672 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1294 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DAB2IPNM_001395010.1 linkuse as main transcriptc.595C>A p.Arg199= synonymous_variant 5/16 ENST00000408936.8
DAB2IPNM_032552.4 linkuse as main transcriptc.511C>A p.Arg171= synonymous_variant 5/17
DAB2IPNM_138709.2 linkuse as main transcriptc.223C>A p.Arg75= synonymous_variant 3/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DAB2IPENST00000408936.8 linkuse as main transcriptc.595C>A p.Arg199= synonymous_variant 5/165 NM_001395010.1 A1Q5VWQ8-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00850
AC:
1294
AN:
152168
Hom.:
14
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0254
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00268
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00308
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.0138
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00671
GnomAD3 exomes
AF:
0.00317
AC:
788
AN:
248220
Hom.:
9
AF XY:
0.00276
AC XY:
370
AN XY:
133924
show subpopulations
Gnomad AFR exome
AF:
0.0254
Gnomad AMR exome
AF:
0.00111
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00334
Gnomad SAS exome
AF:
0.00108
Gnomad FIN exome
AF:
0.0103
Gnomad NFE exome
AF:
0.000267
Gnomad OTH exome
AF:
0.000661
GnomAD4 exome
AF:
0.00135
AC:
1975
AN:
1460584
Hom.:
14
Cov.:
31
AF XY:
0.00131
AC XY:
948
AN XY:
726338
show subpopulations
Gnomad4 AFR exome
AF:
0.0251
Gnomad4 AMR exome
AF:
0.00123
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00436
Gnomad4 SAS exome
AF:
0.000993
Gnomad4 FIN exome
AF:
0.00958
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.00262
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00856
AC:
1304
AN:
152286
Hom.:
14
Cov.:
33
AF XY:
0.00903
AC XY:
672
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0256
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00309
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.0138
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00664
Alfa
AF:
0.00285
Hom.:
1
Bravo
AF:
0.00870
Asia WGS
AF:
0.00953
AC:
33
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.15
Cadd
Benign
9.5
Dann
Benign
0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs114266755; hg19: chr9-124521255; API