chr5-76626679-C-T

Variant names:

• chr5-76626679-C-T
• rs1697845
• NM_006633.5:c.1522-731C>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.1522-731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,966 control chromosomes in the GnomAD database, including 31,706 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 0.64 (31706 hom., cov: 31)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.661 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	NM_006633.5	MANE Select	c.1522-731C>T		intron	N/A	NP_006624.3
	IQGAP2	NM_001285460.2		c.1372-731C>T		intron	N/A	NP_001272389.2
	IQGAP2	NM_001285461.2		c.181-731C>T		intron	N/A	NP_001272390.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.1522-731C>T		intron	N/A	ENSP00000274364.6
	IQGAP2	ENST00000396234.7	TSL:1	c.181-731C>T		intron	N/A	ENSP00000379535.3
	IQGAP2	ENST00000514350.5	TSL:1	c.1441-731C>T		intron	N/A	ENSP00000423672.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97787 AN: 151848 Hom.: 31691 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.644 AC: 97840 AN: 151966 Hom.: 31706 Cov.: 31 AF XY: 0.641 AC XY: 47617 AN XY: 74274

African (AFR) AF: 0.664 AC: 27492 AN: 41424

American (AMR) AF: 0.574 AC: 8771 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2472 AN: 5162

South Asian (SAS) AF: 0.680 AC: 3271 AN: 4808

European-Finnish (FIN) AF: 0.617 AC: 6507 AN: 10538

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44805 AN: 67982

Other (OTH) AF: 0.662 AC: 1388 AN: 2098

Alfa AF: 0.652 Hom.: 91453

Bravo AF: 0.637

Asia WGS AF: 0.545 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.61
PhyloP100		-1.4
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: rs1697845; hg19: chr5-75922504;