5-76588909-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113

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 -15 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_single_submitter, 1 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	UniProt
IQGAP2	NM_006633.5	c.462G>A	p.Leu154=	synonymous_variant	6/36	ENST00000274364.11

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86293 AN: 151880 Hom.: 25495 Cov.: 32

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

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.: 25 AF XY: 0.509 AC XY: 362999 AN XY: 713668

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.: 32 AF XY: 0.572 AC XY: 42523 AN XY: 74304

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 11, 2018

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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

Other links and lift over

dbSNP: rs1131232; hg19: chr5-75884734; COSMIC: COSV57170100;