chr5-76570598-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006633.5(IQGAP2):​c.322C>T​(p.Arg108Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000377 in 1,613,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

IQGAP2
NM_006633.5 stop_gained

Scores

5
1
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
IQGAP2 (HGNC:6111): (IQ motif containing GTPase activating protein 2) This gene encodes a member of the IQGAP family. The encoded protein contains three IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. This protein interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. It also acts as a tumor suppressor and has been found to play a role in regulating innate antiviral responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IQGAP2NM_006633.5 linkuse as main transcriptc.322C>T p.Arg108Ter stop_gained 4/36 ENST00000274364.11 NP_006624.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IQGAP2ENST00000274364.11 linkuse as main transcriptc.322C>T p.Arg108Ter stop_gained 4/361 NM_006633.5 ENSP00000274364 P1Q13576-1
IQGAP2ENST00000514350.5 linkuse as main transcriptc.241C>T p.Arg81Ter stop_gained 4/221 ENSP00000423672
IQGAP2ENST00000379730.7 linkuse as main transcriptc.172C>T p.Arg58Ter stop_gained 3/355 ENSP00000442313

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000221
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251364
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000404
AC:
590
AN:
1460994
Hom.:
0
Cov.:
29
AF XY:
0.000392
AC XY:
285
AN XY:
726886
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.000506
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000200
Hom.:
0
Bravo
AF:
0.000159
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

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 submitterclinical testingGenomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of PhiladelphiaNov 06, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
46
DANN
Uncertain
1.0
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A;D
Vest4
0.80
GERP RS
5.5

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs192694811; hg19: chr5-75866423; COSMIC: COSV57168838; API