rs3797418

Variant names:

• chr5-76639589-G-T
• rs3797418
• NM_006633.5:c.1924-1344G>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.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
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.29 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.1924-1344G>T		intron	N/A	NP_006624.3	Q13576-1
	IQGAP2	NM_001285460.2		c.1774-1344G>T		intron	N/A	NP_001272389.2	F5H7S7
	IQGAP2	NM_001285461.2		c.582+2413G>T		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.1924-1344G>T		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000396234.7	TSL:1	c.582+2413G>T		intron	N/A	ENSP00000379535.3	Q13576-2
	IQGAP2	ENST00000514350.5	TSL:1	c.1843-1344G>T		intron	N/A	ENSP00000423672.1	D6R939

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

African (AFR) AF: 0.0528 AC: 2193 AN: 41522

American (AMR) AF: 0.198 AC: 3028 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5186

South Asian (SAS) AF: 0.241 AC: 1164 AN: 4824

European-Finnish (FIN) AF: 0.267 AC: 2818 AN: 10548

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19922 AN: 67950

Other (OTH) AF: 0.222 AC: 468 AN: 2110

Alfa AF: 0.258 Hom.: 3820

Bravo AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.63
PhyloP100		0.16
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: rs3797418; hg19: chr5-75935414;