rs9293692

Positions:

• chr5-76658088-C-G

Variant summary

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

The NM_006633.5(IQGAP2):​c.2321-371C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,066 control chromosomes in the GnomAD database, including 1,428 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 0.12 (1428 hom., cov: 32)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP2	NM_006633.5	c.2321-371C>G		intron_variant		ENST00000274364.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP2	ENST00000274364.11	c.2321-371C>G		intron_variant		1	NM_006633.5	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18515 AN: 151946 Hom.: 1430 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.122 AC: 18517 AN: 152066 Hom.: 1428 Cov.: 32 AF XY: 0.118 AC XY: 8804 AN XY: 74350

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.148

Alfa AF: 0.149 Hom.: 260

Bravo AF: 0.118

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9293692; hg19: chr5-75953913;