5-76623406-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006633.5(IQGAP2):c.1522-4004T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 644,724 control chromosomes in the GnomAD database, including 49 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 0.012 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (11 hom.)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

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]

F2RL2 (HGNC:3539): (coagulation factor II thrombin receptor like 2) This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1756/152376) while in subpopulation AFR AF= 0.0404 (1680/41600). AF 95% confidence interval is 0.0388. There are 38 homozygotes in gnomad4. There are 817 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1739 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP2	NM_006633.5	c.1522-4004T>G		intron_variant		ENST00000274364.11
F2RL2	NM_004101.4			upstream_gene_variant		ENST00000296641.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP2	ENST00000274364.11	c.1522-4004T>G		intron_variant		1	NM_006633.5	P1
F2RL2	ENST00000296641.5			upstream_gene_variant		1	NM_004101.4	P2

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1739 AN: 152258 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00139 AC: 683 AN: 492348 Hom.: 11 Cov.: 6 AF XY: 0.00116 AC XY: 300 AN XY: 258916

Gnomad4 AFR exome AF: 0.0390

Gnomad4 AMR exome AF: 0.00294

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000217

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000457

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.0115 AC: 1756 AN: 152376 Hom.: 38 Cov.: 33 AF XY: 0.0110 AC XY: 817 AN XY: 74528

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00140 Hom.: 1

Bravo AF: 0.0132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	6.3
Dann	Benign	0.69

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: rs2069647; hg19: chr5-75919231;