Variant 5-76590467-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.360

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]

IQGAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 621 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP2	NM_006633.5 linkuse as main transcript	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 linkuse as main transcript	c.700G>A	p.Val234Ile	missense_variant	8/36	1	NM_006633.5	P1	Q13576-1
IQGAP2	ENST00000514350.5 linkuse as main transcript	c.619G>A	p.Val207Ile	missense_variant	8/22	1
IQGAP2	ENST00000379730.7 linkuse as main transcript	c.550G>A	p.Val184Ile	missense_variant	7/35	5

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

623

AN:

152160

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00705

AC XY:

957

AN XY:

135710

show subpopulations

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.:

Cov.:

AF XY:

0.00542

AC XY:

3939

AN XY:

727022

show subpopulations

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.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74442

show subpopulations

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.:

Bravo

AF:

0.00389

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00623

AC:

756

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00464

EpiControl

AF:

0.00611

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.63

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

LIST_S2

Benign

0.70

T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.095

N;.;.;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.26

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

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over