GeneBe

rs2577126

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012414.4(RAB3GAP2):ā€‹c.2088A>Gā€‹(p.Thr696=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,613,554 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.034 ( 286 hom., cov: 32)
Exomes š‘“: 0.0038 ( 266 hom. )

Consequence

RAB3GAP2
NM_012414.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.613
Variant links:
Genes affected
RAB3GAP2 (HGNC:17168): (RAB3 GTPase activating non-catalytic protein subunit 2) The protein encoded by this gene belongs to the RAB3 protein family, members of which are involved in regulated exocytosis of neurotransmitters and hormones. This protein forms the Rab3 GTPase-activating complex with RAB3GAP1, where it constitutes the regulatory subunit, whereas the latter functions as the catalytic subunit. This gene has the highest level of expression in the brain, consistent with it having a key role in neurodevelopment. Mutations in this gene are associated with Martsolf syndrome.[provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 1-220182842-T-C is Benign according to our data. Variant chr1-220182842-T-C is described in ClinVar as [Benign]. Clinvar id is 130077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-220182842-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.613 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAB3GAP2NM_012414.4 linkuse as main transcriptc.2088A>G p.Thr696= synonymous_variant 20/35 ENST00000358951.7 NP_036546.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAB3GAP2ENST00000358951.7 linkuse as main transcriptc.2088A>G p.Thr696= synonymous_variant 20/351 NM_012414.4 ENSP00000351832 P2Q9H2M9-1

Frequencies

GnomAD3 genomes
AF:
0.0337
AC:
5135
AN:
152200
Hom.:
287
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.116
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0131
Gnomad ASJ
AF:
0.0161
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.0201
GnomAD3 exomes
AF:
0.00941
AC:
2363
AN:
251194
Hom.:
124
AF XY:
0.00729
AC XY:
990
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.118
Gnomad AMR exome
AF:
0.00634
Gnomad ASJ exome
AF:
0.0137
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.0000925
Gnomad NFE exome
AF:
0.000519
Gnomad OTH exome
AF:
0.00523
GnomAD4 exome
AF:
0.00378
AC:
5518
AN:
1461236
Hom.:
266
Cov.:
31
AF XY:
0.00335
AC XY:
2439
AN XY:
726982
show subpopulations
Gnomad4 AFR exome
AF:
0.118
Gnomad4 AMR exome
AF:
0.00682
Gnomad4 ASJ exome
AF:
0.0134
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.000300
Gnomad4 NFE exome
AF:
0.000291
Gnomad4 OTH exome
AF:
0.00840
GnomAD4 genome
AF:
0.0337
AC:
5129
AN:
152318
Hom.:
286
Cov.:
32
AF XY:
0.0331
AC XY:
2463
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.115
Gnomad4 AMR
AF:
0.0131
Gnomad4 ASJ
AF:
0.0161
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.0198
Alfa
AF:
0.0181
Hom.:
65
Bravo
AF:
0.0386
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.000872
EpiControl
AF:
0.00107

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitterclinical testingGeneDxApr 28, 2014This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Warburg micro syndrome 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Martsolf syndrome;C3280214:Warburg micro syndrome 2 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Martsolf syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
3.9
DANN
Benign
0.69

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: rs2577126; hg19: chr1-220356184; API