chr15-90388391-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003870.4(IQGAP1):c.50A>G(p.Tyr17Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,371,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
IQGAP1
NM_003870.4 missense
NM_003870.4 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 4.84
Genes affected
IQGAP1 (HGNC:6110): (IQ motif containing GTPase activating protein 1) This gene encodes a member of the IQGAP family. The protein contains four IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. It interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. Expression of the protein is upregulated by gene amplification in two gastric cancer cell lines. [provided by RefSeq, Jul 2008]
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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 |
---|---|---|---|---|---|---|---|
IQGAP1 | NM_003870.4 | c.50A>G | p.Tyr17Cys | missense_variant | 1/38 | ENST00000268182.10 | |
IQGAP1 | XM_047433204.1 | c.50A>G | p.Tyr17Cys | missense_variant | 1/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQGAP1 | ENST00000268182.10 | c.50A>G | p.Tyr17Cys | missense_variant | 1/38 | 1 | NM_003870.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 148764Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000477 AC: 1AN: 209516Hom.: 0 AF XY: 0.00000853 AC XY: 1AN XY: 117282
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GnomAD4 exome AF: 7.29e-7 AC: 1AN: 1371662Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 682620
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 148764Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72630
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Data not reliable, filtered out with message: AC0
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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 | Sep 01, 2021 | The c.50A>G (p.Y17C) alteration is located in exon 1 (coding exon 1) of the IQGAP1 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the tyrosine (Y) at amino acid position 17 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;T
Sift4G
Uncertain
D;T
Polyphen
D;.
Vest4
MutPred
Loss of phosphorylation at Y17 (P = 0.0205);Loss of phosphorylation at Y17 (P = 0.0205);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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