rs3885957

Variant names:

• chr5-76552568-T-C
• rs3885957
• NM_006633.5:c.147-9828T>C

Variant summary

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

The NM_006633.5(IQGAP2):​c.147-9828T>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
• Publications: 2 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=-0.92).
• 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 rank	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.147-9828T>C		intron_variant	Intron 2 of 35	ENST00000274364.11	NP_006624.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.147-9828T>C		intron_variant	Intron 2 of 35	1	NM_006633.5	ENSP00000274364.6
IQGAP2	ENST00000514350.5	c.66-9828T>C		intron_variant	Intron 2 of 21	1		ENSP00000423672.1
IQGAP2	ENST00000379730.7	c.-5+5117T>C		intron_variant	Intron 1 of 34	5		ENSP00000442313.2

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

African (AFR) AF: 0.228 AC: 9488 AN: 41524

American (AMR) AF: 0.151 AC: 2315 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3468

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5186

South Asian (SAS) AF: 0.394 AC: 1898 AN: 4820

European-Finnish (FIN) AF: 0.163 AC: 1726 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14915 AN: 67990

Other (OTH) AF: 0.216 AC: 456 AN: 2110

Alfa AF: 0.207 Hom.: 652

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
PhyloP100		-0.62
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: rs3885957; hg19: chr5-75848393;