rs457717

Variant names:

• chr5-76625147-A-G
• rs457717
• NM_006633.5:c.1522-2263A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-76625147-A-G
• chr5-76625147-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006633.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	NM_006633.5	MANE Select	c.1522-2263A>G		intron	N/A	NP_006624.3	Q13576-1
	IQGAP2	NM_001285460.2		c.1372-2263A>G		intron	N/A	NP_001272389.2	F5H7S7
	IQGAP2	NM_001285461.2		c.181-2263A>G		intron	N/A	NP_001272390.2	Q13576-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.1522-2263A>G		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000396234.7	TSL:1	c.181-2263A>G		intron	N/A	ENSP00000379535.3	Q13576-2
	IQGAP2	ENST00000514350.5	TSL:1	c.1441-2263A>G		intron	N/A	ENSP00000423672.1	D6R939

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

African (AFR) AF: 0.671 AC: 27842 AN: 41492

American (AMR) AF: 0.586 AC: 8960 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2486 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2485 AN: 5168

South Asian (SAS) AF: 0.681 AC: 3287 AN: 4824

European-Finnish (FIN) AF: 0.625 AC: 6608 AN: 10568

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45402 AN: 67982

Other (OTH) AF: 0.673 AC: 1422 AN: 2114

Alfa AF: 0.656 Hom.: 52015

Bravo AF: 0.646

Asia WGS AF: 0.549 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.29
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs457717; hg19: chr5-75920972; COSMIC: COSV107278827; COSMIC: COSV107278827;