rs457717

chr5-76625147-A-Gchr5-76625147-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006633.5(IQGAP2):c.1522-2263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,106 control chromosomes in the GnomAD database, including 32,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32584 hom., cov: 32)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP2	NM_006633.5	c.1522-2263A>G		intron_variant		ENST00000274364.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP2	ENST00000274364.11	c.1522-2263A>G		intron_variant		1	NM_006633.5	P1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99143 AN: 151988 Hom.: 32568 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.675

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99194 AN: 152106 Hom.: 32584 Cov.: 32 AF XY: 0.649 AC XY: 48258 AN XY: 74344

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.673

Alfa AF: 0.655 Hom.: 24388

Bravo AF: 0.646

Asia WGS AF: 0.549 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.13
Dann	Benign	0.29

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: rs457717; hg19: chr5-75920972;