5-76632129-A-G

Position:

• chr5-76632129-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP2	NM_006633.5	c.1780+103A>G		intron_variant		ENST00000274364.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP2	ENST00000274364.11	c.1780+103A>G		intron_variant		1	NM_006633.5	P1

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

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.287

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

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.259

Alfa AF: 0.284 Hom.: 1481

Bravo AF: 0.253

Asia WGS AF: 0.354 AC: 1227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.86

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: rs3797412; hg19: chr5-75927954;