chr5-76461582-A-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006633.5(IQGAP2):c.59A>T(p.Asp20Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000595 in 1,613,236 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
IQGAP2
NM_006633.5 missense
NM_006633.5 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 7.19
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IQGAP2 | NM_006633.5 | c.59A>T | p.Asp20Val | missense_variant | 2/36 | ENST00000274364.11 | NP_006624.3 | |
IQGAP2 | XM_047416641.1 | c.134A>T | p.Asp45Val | missense_variant | 2/36 | XP_047272597.1 | ||
IQGAP2 | XM_017008960.2 | c.59A>T | p.Asp20Val | missense_variant | 2/35 | XP_016864449.1 | ||
IQGAP2 | XM_005248410.4 | c.-23A>T | 5_prime_UTR_variant | 2/36 | XP_005248467.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IQGAP2 | ENST00000274364.11 | c.59A>T | p.Asp20Val | missense_variant | 2/36 | 1 | NM_006633.5 | ENSP00000274364 | P1 | |
IQGAP2 | ENST00000514350.5 | c.-23A>T | 5_prime_UTR_variant | 2/22 | 1 | ENSP00000423672 | ||||
IQGAP2 | ENST00000692467.1 | n.260A>T | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251160Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135724
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1460942Hom.: 0 Cov.: 29 AF XY: 0.0000715 AC XY: 52AN XY: 726884
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74470
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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 25, 2024 | The c.59A>T (p.D20V) alteration is located in exon 2 (coding exon 2) of the IQGAP2 gene. This alteration results from a A to T substitution at nucleotide position 59, causing the aspartic acid (D) at amino acid position 20 to be replaced by a valine (V). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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