chr5-76562470-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006633.5(IQGAP2):​c.221A>T​(p.Tyr74Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IQGAP2
NM_006633.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37919408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IQGAP2NM_006633.5 linkuse as main transcriptc.221A>T p.Tyr74Phe missense_variant 3/36 ENST00000274364.11 NP_006624.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IQGAP2ENST00000274364.11 linkuse as main transcriptc.221A>T p.Tyr74Phe missense_variant 3/361 NM_006633.5 ENSP00000274364 P1Q13576-1
IQGAP2ENST00000514350.5 linkuse as main transcriptc.140A>T p.Tyr47Phe missense_variant 3/221 ENSP00000423672
IQGAP2ENST00000379730.7 linkuse as main transcriptc.71A>T p.Tyr24Phe missense_variant 2/355 ENSP00000442313

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251432
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461686
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsSep 23, 2023The c.221A>T (p.Y74F) alteration is located in exon 3 (coding exon 3) of the IQGAP2 gene. This alteration results from a A to T substitution at nucleotide position 221, causing the tyrosine (Y) at amino acid position 74 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.57
D;T;.;.
Eigen
Benign
-0.011
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.38
T;T;T;T
MetaSVM
Uncertain
0.29
D
MutationAssessor
Benign
1.1
L;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-2.1
N;D;N;.
REVEL
Uncertain
0.38
Sift
Benign
0.056
T;T;T;.
Sift4G
Benign
0.32
T;T;T;T
Polyphen
0.12
B;.;.;.
Vest4
0.38
MutPred
0.47
Gain of methylation at K77 (P = 0.0854);.;.;.;
MVP
0.82
MPC
0.24
ClinPred
0.15
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.21
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779912911; hg19: chr5-75858295; API