Variant 5-76588909-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006633.5(IQGAP2):c.462G>A(p.Leu154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,583,014 control chromosomes in the GnomAD database, including 214,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25514 hom., cov: 32)

Exomes 𝑓: 0.50 ( 188827 hom. )

Consequence

IQGAP2
NM_006633.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.113

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 5-76588909-G-A is Benign according to our data. Variant chr5-76588909-G-A is described in ClinVar as [Benign]. Clinvar id is 1232742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.113 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP2	NM_006633.5 linkuse as main transcript	c.462G>A	p.Leu154=	synonymous_variant	6/36	ENST00000274364.11	NP_006624.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11 linkuse as main transcript	c.462G>A	p.Leu154=	synonymous_variant	6/36	1	NM_006633.5	ENSP00000274364	P1	Q13576-1
IQGAP2	ENST00000514350.5 linkuse as main transcript	c.381G>A	p.Leu127=	synonymous_variant	6/22	1		ENSP00000423672
IQGAP2	ENST00000379730.7 linkuse as main transcript	c.312G>A	p.Leu104=	synonymous_variant	5/35	5		ENSP00000442313

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86293

AN:

151880

Hom.:

25495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.544

GnomAD3 exomes

AF:

0.575

AC:

142563

AN:

247978

Hom.:

42971

AF XY:

0.572

AC XY:

76757

AN XY:

134108

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.691

Gnomad ASJ exome

AF:

0.577

Gnomad EAS exome

AF:

0.739

Gnomad SAS exome

AF:

0.737

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.503

AC:

720501

AN:

1431016

Hom.:

188827

Cov.:

AF XY:

0.509

AC XY:

362999

AN XY:

713668

show subpopulations

Gnomad4 AFR exome

AF:

0.708

Gnomad4 AMR exome

AF:

0.677

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.462

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.568

AC:

86365

AN:

151998

Hom.:

25514

Cov.:

AF XY:

0.572

AC XY:

42523

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.605

Gnomad4 ASJ

AF:

0.579

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.752

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.506

Hom.:

11212

Bravo

AF:

0.581

Asia WGS

AF:

0.701

AC:

2435

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.6

DANN

Benign

0.64

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