chr5-76562437-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_006633.5(IQGAP2):c.188C>T(p.Thr63Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,696 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 (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
IQGAP2
NM_006633.5 missense
NM_006633.5 missense
Scores
11
4
4
Clinical Significance
Conservation
PhyloP100: 7.90
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 -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.832
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IQGAP2 | NM_006633.5 | c.188C>T | p.Thr63Ile | missense_variant | 3/36 | ENST00000274364.11 | NP_006624.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IQGAP2 | ENST00000274364.11 | c.188C>T | p.Thr63Ile | missense_variant | 3/36 | 1 | NM_006633.5 | ENSP00000274364 | P1 | |
IQGAP2 | ENST00000514350.5 | c.107C>T | p.Thr36Ile | missense_variant | 3/22 | 1 | ENSP00000423672 | |||
IQGAP2 | ENST00000379730.7 | c.38C>T | p.Thr13Ile | missense_variant | 2/35 | 5 | ENSP00000442313 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
2
AN:
152102
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251248Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135804
GnomAD3 exomes
AF:
AC:
3
AN:
251248
Hom.:
AF XY:
AC XY:
3
AN XY:
135804
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461594Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727100
GnomAD4 exome
AF:
AC:
5
AN:
1461594
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727100
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74292
GnomAD4 genome
AF:
AC:
2
AN:
152102
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74292
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
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 | Jul 17, 2023 | The c.188C>T (p.T63I) alteration is located in exon 3 (coding exon 3) of the IQGAP2 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the threonine (T) at amino acid position 63 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;.
REVEL
Pathogenic
Sift
Benign
T;D;T;.
Sift4G
Benign
T;T;T;T
Polyphen
D;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0293);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at