chr5-76592923-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006633.5(IQGAP2):c.905A>C(p.Asn302Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,435,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
IQGAP2
NM_006633.5 missense, splice_region
NM_006633.5 missense, splice_region
Scores
4
10
5
Splicing: ADA: 0.8533
2
Clinical Significance
Conservation
PhyloP100: 9.29
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQGAP2 | NM_006633.5 | c.905A>C | p.Asn302Thr | missense_variant, splice_region_variant | 9/36 | ENST00000274364.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQGAP2 | ENST00000274364.11 | c.905A>C | p.Asn302Thr | missense_variant, splice_region_variant | 9/36 | 1 | NM_006633.5 | P1 | |
IQGAP2 | ENST00000514350.5 | c.824A>C | p.Asn275Thr | missense_variant, splice_region_variant | 9/22 | 1 | |||
IQGAP2 | ENST00000379730.7 | c.755A>C | p.Asn252Thr | missense_variant, splice_region_variant | 8/35 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000348 AC: 5AN: 1435364Hom.: 0 Cov.: 25 AF XY: 0.00000279 AC XY: 2AN XY: 715916
GnomAD4 exome
AF:
AC:
5
AN:
1435364
Hom.:
Cov.:
25
AF XY:
AC XY:
2
AN XY:
715916
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
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EpiControl
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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 | Mar 11, 2022 | The c.905A>C (p.N302T) alteration is located in exon 9 (coding exon 9) of the IQGAP2 gene. This alteration results from a A to C substitution at nucleotide position 905, causing the asparagine (N) at amino acid position 302 to be replaced by a threonine (T). 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
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;.
Sift4G
Uncertain
D;D;D;D
Polyphen
P;.;.;.
Vest4
MutPred
Gain of methylation at K300 (P = 0.1628);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at