5-76590467-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006633.5(IQGAP2):c.700G>A(p.Val234Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,613,768 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (53 hom.)
• Consequence: IQGAP2 NM_006633.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035094917).
• BP6: Variant 5-76590467-G-A is Benign according to our data. Variant chr5-76590467-G-A is described in ClinVar as [Benign]. Clinvar id is 720792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00493 (7209/1461490) while in subpopulation SAS AF= 0.0158 (1358/86186). AF 95% confidence interval is 0.0151. There are 53 homozygotes in gnomad4_exome. There are 3939 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 623 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP2	NM_006633.5	c.700G>A	p.Val234Ile	missense_variant	8/36	ENST00000274364.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP2	ENST00000274364.11	c.700G>A	p.Val234Ile	missense_variant	8/36	1	NM_006633.5	P1
IQGAP2	ENST00000514350.5	c.619G>A	p.Val207Ile	missense_variant	8/22	1
IQGAP2	ENST00000379730.7	c.550G>A	p.Val184Ile	missense_variant	7/35	5

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 623 AN: 152160 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00656 AC: 1648 AN: 251124 Hom.: 18 AF XY: 0.00705 AC XY: 957 AN XY: 135710

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.0160

Gnomad EAS exome AF: 0.0168

Gnomad SAS exome AF: 0.0166

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00735

GnomAD4 exome AF: 0.00493 AC: 7209 AN: 1461490 Hom.: 53 Cov.: 31 AF XY: 0.00542 AC XY: 3939 AN XY: 727022

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.00365

Gnomad4 ASJ exome AF: 0.0159

Gnomad4 EAS exome AF: 0.00885

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00802

GnomAD4 genome AF: 0.00408 AC: 621 AN: 152278 Hom.: 6 Cov.: 33 AF XY: 0.00399 AC XY: 297 AN XY: 74442

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00373

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00512 Hom.: 8

Bravo AF: 0.00389

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00623 AC: 756

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.00464

EpiControl AF: 0.00611

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.24
Dann	Benign	0.84
DEOGEN2	Benign	0.064	T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.70	T;T;T;T
MetaRNN	Benign	0.0035	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.095	N;.;.;.
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.46	N;N;N;.
REVEL	Benign	0.012
Sift	Benign	0.24	T;T;T;.
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.076
MVP		0.19
MPC		0.14
ClinPred		0.00057	T
GERP RS		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.016
gMVP		0.12

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

Other links and lift over

dbSNP: rs147531108; hg19: chr5-75886292; COSMIC: COSV57170959;