rs3797418

Positions:

• chr5-76639589-G-T

Variant summary

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

The NM_006633.5(IQGAP2):​c.1924-1344G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,098 control chromosomes in the GnomAD database, including 4,089 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 0.20 (4089 hom., cov: 33)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.1924-1344G>T		intron_variant		ENST00000274364.11	NP_006624.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.1924-1344G>T		intron_variant		1	NM_006633.5	ENSP00000274364.6

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30895 AN: 151980 Hom.: 4087 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.203 AC: 30893 AN: 152098 Hom.: 4089 Cov.: 33 AF XY: 0.202 AC XY: 14992 AN XY: 74338

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.222

Alfa AF: 0.268 Hom.: 2745

Bravo AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.63

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: rs3797418; hg19: chr5-75935414;