5-76588909-G-A

Variant names:

• chr5-76588909-G-A
• rs1131232
• NM_006633.5:c.462G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006633.5(IQGAP2):​c.462G>A​(p.Leu154Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,583,014 control chromosomes in the GnomAD database, including 214,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25514 hom., cov: 32)
  • Exomes 𝑓: 0.50 (188827 hom.)
• Consequence: IQGAP2 NM_006633.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.113
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 5-76588909-G-A is Benign according to our data. Variant chr5-76588909-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 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.462G>A	p.Leu154Leu	synonymous	Exon 6 of 36	NP_006624.3	Q13576-1
	IQGAP2	NM_001285460.2		c.312G>A	p.Leu104Leu	synonymous	Exon 5 of 35	NP_001272389.2	F5H7S7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.462G>A	p.Leu154Leu	synonymous	Exon 6 of 36	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000514350.5	TSL:1	c.381G>A	p.Leu127Leu	synonymous	Exon 6 of 22	ENSP00000423672.1	D6R939
	IQGAP2	ENST00000379730.7	TSL:5	c.312G>A	p.Leu104Leu	synonymous	Exon 5 of 35	ENSP00000442313.2	F5H7S7

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86293 AN: 151880 Hom.: 25495 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.575 AC: 142563 AN: 247978 AF XY: 0.572

Gnomad AFR exome AF: 0.709

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.577

Gnomad EAS exome AF: 0.739

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.471

Gnomad OTH exome AF: 0.539

GnomAD4 exome AF: 0.503 AC: 720501 AN: 1431016 Hom.: 188827 Cov.: 25 AF XY: 0.509 AC XY: 362999 AN XY: 713668

African (AFR) AF: 0.708 AC: 23055 AN: 32586

American (AMR) AF: 0.677 AC: 29886 AN: 44114

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 14850 AN: 25822

East Asian (EAS) AF: 0.736 AC: 28871 AN: 39234

South Asian (SAS) AF: 0.734 AC: 62355 AN: 84956

European-Finnish (FIN) AF: 0.482 AC: 25669 AN: 53202

Middle Eastern (MID) AF: 0.578 AC: 3292 AN: 5696

European-Non Finnish (NFE) AF: 0.462 AC: 501416 AN: 1086236

Other (OTH) AF: 0.526 AC: 31107 AN: 59170

GnomAD4 genome AF: 0.568 AC: 86365 AN: 151998 Hom.: 25514 Cov.: 32 AF XY: 0.572 AC XY: 42523 AN XY: 74304

African (AFR) AF: 0.701 AC: 29060 AN: 41446

American (AMR) AF: 0.605 AC: 9241 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3935 AN: 5182

South Asian (SAS) AF: 0.752 AC: 3626 AN: 4822

European-Finnish (FIN) AF: 0.471 AC: 4973 AN: 10548

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31651 AN: 67936

Other (OTH) AF: 0.540 AC: 1141 AN: 2112

Alfa AF: 0.516 Hom.: 16631

Bravo AF: 0.581

Asia WGS AF: 0.701 AC: 2435 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		0.11
Mutation Taster		=296/4	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: rs1131232; hg19: chr5-75884734; COSMIC: COSV57170100;