chr5-76590473-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006633.5(IQGAP2):c.706A>T(p.Thr236Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
IQGAP2
NM_006633.5 missense
NM_006633.5 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 3.99
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.22120756).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQGAP2 | NM_006633.5 | c.706A>T | p.Thr236Ser | missense_variant | 8/36 | ENST00000274364.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQGAP2 | ENST00000274364.11 | c.706A>T | p.Thr236Ser | missense_variant | 8/36 | 1 | NM_006633.5 | P1 | |
IQGAP2 | ENST00000514350.5 | c.625A>T | p.Thr209Ser | missense_variant | 8/22 | 1 | |||
IQGAP2 | ENST00000379730.7 | c.556A>T | p.Thr186Ser | missense_variant | 7/35 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251216Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135760
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727140
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
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Cov.:
33
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 08, 2021 | The c.706A>T (p.T236S) alteration is located in exon 8 (coding exon 8) of the IQGAP2 gene. This alteration results from a A to T substitution at nucleotide position 706, causing the threonine (T) at amino acid position 236 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Benign
T;D;T;.
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;.
Vest4
MutPred
Gain of helix (P = 0.0854);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at