rs3885957

Positions:

• chr5-76552568-T-C

Variant summary

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

The NM_006633.5(IQGAP2):​c.147-9828T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,188 control chromosomes in the GnomAD database, including 3,595 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 0.21 (3595 hom., cov: 32)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.147-9828T>C		intron_variant		ENST00000274364.11	NP_006624.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.147-9828T>C		intron_variant		1	NM_006633.5	ENSP00000274364	P1
IQGAP2	ENST00000514350.5	c.66-9828T>C		intron_variant		1		ENSP00000423672
IQGAP2	ENST00000379730.7	c.-5+5117T>C		intron_variant		5		ENSP00000442313

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32245 AN: 152070 Hom.: 3594 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.0167

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.212 AC: 32252 AN: 152188 Hom.: 3595 Cov.: 32 AF XY: 0.211 AC XY: 15725 AN XY: 74414

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.216

Alfa AF: 0.207 Hom.: 635

Bravo AF: 0.204

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.72

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: rs3885957; hg19: chr5-75848393;