rs4704327

Variant names:

• chr5-76540207-A-G
• rs4704327
• NM_006633.5:c.147-22189A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006633.5(IQGAP2):​c.147-22189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,214 control chromosomes in the GnomAD database, including 1,970 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 0.15 (1970 hom., cov: 32)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.147-22189A>G		intron_variant	Intron 2 of 35	ENST00000274364.11	NP_006624.3
IQGAP2	XM_047416641.1	c.222-22189A>G		intron_variant	Intron 2 of 35		XP_047272597.1
IQGAP2	XM_005248410.4	c.66-22189A>G		intron_variant	Intron 2 of 35		XP_005248467.1
IQGAP2	XM_017008960.2	c.147-22189A>G		intron_variant	Intron 2 of 34		XP_016864449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.147-22189A>G		intron_variant	Intron 2 of 35	1	NM_006633.5	ENSP00000274364.6
IQGAP2	ENST00000514350.5	c.66-22189A>G		intron_variant	Intron 2 of 21	1		ENSP00000423672.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23525 AN: 152096 Hom.: 1970 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.155 AC: 23549 AN: 152214 Hom.: 1970 Cov.: 32 AF XY: 0.156 AC XY: 11609 AN XY: 74420

African (AFR) AF: 0.152 AC: 6295 AN: 41512

American (AMR) AF: 0.275 AC: 4196 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.0727 AC: 377 AN: 5188

South Asian (SAS) AF: 0.112 AC: 543 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1622 AN: 10602

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9528 AN: 68016

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.164 Hom.: 391

Bravo AF: 0.165

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.59
PhyloP100		-0.33
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: rs4704327; hg19: chr5-75836032;