5-76632129-A-G

Variant names:

• chr5-76632129-A-G
• rs3797412
• NM_006633.5:c.1780+103A>G

Variant summary

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

The NM_006633.5(IQGAP2):​c.1780+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 991,388 control chromosomes in the GnomAD database, including 43,647 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 0.27 (5651 hom., cov: 32)
  • Exomes 𝑓: 0.30 (37996 hom.)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 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.1780+103A>G		intron	N/A	NP_006624.3	Q13576-1
	IQGAP2	NM_001285460.2		c.1630+103A>G		intron	N/A	NP_001272389.2	F5H7S7
	IQGAP2	NM_001285461.2		c.439+103A>G		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.1780+103A>G		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000396234.7	TSL:1	c.439+103A>G		intron	N/A	ENSP00000379535.3	Q13576-2
	IQGAP2	ENST00000514350.5	TSL:1	c.1699+103A>G		intron	N/A	ENSP00000423672.1	D6R939

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40350 AN: 151994 Hom.: 5652 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.297 AC: 249188 AN: 839274 Hom.: 37996 AF XY: 0.297 AC XY: 124652 AN XY: 419300

African (AFR) AF: 0.173 AC: 2919 AN: 16876

American (AMR) AF: 0.206 AC: 3101 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 4244 AN: 15790

East Asian (EAS) AF: 0.388 AC: 10912 AN: 28126

South Asian (SAS) AF: 0.284 AC: 11879 AN: 41798

European-Finnish (FIN) AF: 0.321 AC: 13842 AN: 43158

Middle Eastern (MID) AF: 0.278 AC: 1101 AN: 3962

European-Non Finnish (NFE) AF: 0.299 AC: 190492 AN: 637278

Other (OTH) AF: 0.287 AC: 10698 AN: 37268

GnomAD4 genome AF: 0.265 AC: 40360 AN: 152114 Hom.: 5651 Cov.: 32 AF XY: 0.266 AC XY: 19809 AN XY: 74358

African (AFR) AF: 0.180 AC: 7473 AN: 41512

American (AMR) AF: 0.215 AC: 3289 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2060 AN: 5170

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3512 AN: 10584

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20804 AN: 67956

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.284 Hom.: 2362

Bravo AF: 0.253

Asia WGS AF: 0.354 AC: 1227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.86
PhyloP100		-0.58
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: rs3797412; hg19: chr5-75927954; COSMIC: COSV107278645; COSMIC: COSV107278645;