chr5-76403565-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006633.5(IQGAP2):​c.20C>A​(p.Pro7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,538,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

IQGAP2
NM_006633.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10539392).
BS2
High AC in GnomAdExome4 at 83 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IQGAP2NM_006633.5 linkuse as main transcriptc.20C>A p.Pro7Gln missense_variant 1/36 ENST00000274364.11 NP_006624.3
IQGAP2XM_017008960.2 linkuse as main transcriptc.20C>A p.Pro7Gln missense_variant 1/35 XP_016864449.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IQGAP2ENST00000274364.11 linkuse as main transcriptc.20C>A p.Pro7Gln missense_variant 1/361 NM_006633.5 ENSP00000274364 P1Q13576-1
IQGAP2ENST00000692467.1 linkuse as main transcriptn.221C>A non_coding_transcript_exon_variant 1/2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151998
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000107
AC:
15
AN:
139724
Hom.:
0
AF XY:
0.000128
AC XY:
10
AN XY:
78264
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000460
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000870
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000599
AC:
83
AN:
1386632
Hom.:
0
Cov.:
30
AF XY:
0.0000729
AC XY:
50
AN XY:
686286
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000870
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000308
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000481
Gnomad4 OTH exome
AF:
0.0000697
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151998
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000469
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000432
AC:
5

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 GeneticsJun 29, 2023The c.20C>A (p.P7Q) alteration is located in exon 1 (coding exon 1) of the IQGAP2 gene. This alteration results from a C to A substitution at nucleotide position 20, causing the proline (P) at amino acid position 7 to be replaced by a glutamine (Q). 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
0.088
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.092
T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.084
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.74
T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.52
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.097
Sift
Benign
0.22
T
Sift4G
Benign
0.45
T
Polyphen
0.53
P
Vest4
0.16
MVP
0.41
MPC
0.18
ClinPred
0.16
T
GERP RS
3.7
Varity_R
0.096
gMVP
0.44

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: rs747881615; hg19: chr5-75699390; API