chr5-76620080-C-G

Variant names:

• chr5-76620080-C-G
• rs950643
• NM_006633.5:c.1522-7330C>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.1522-7330C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,078 control chromosomes in the GnomAD database, including 10,873 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 0.36 (10873 hom., cov: 32)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 2 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]

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.1522-7330C>G		intron_variant	Intron 13 of 35	ENST00000274364.11	NP_006624.3
F2RL2	NM_004101.4	c.65-1438G>C		intron_variant	Intron 1 of 1	ENST00000296641.5	NP_004092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.1522-7330C>G		intron_variant	Intron 13 of 35	1	NM_006633.5	ENSP00000274364.6
F2RL2	ENST00000296641.5	c.65-1438G>C		intron_variant	Intron 1 of 1	1	NM_004101.4	ENSP00000296641.3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54448 AN: 151960 Hom.: 10875 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.358 AC: 54461 AN: 152078 Hom.: 10873 Cov.: 32 AF XY: 0.357 AC XY: 26500 AN XY: 74320

African (AFR) AF: 0.195 AC: 8095 AN: 41508

American (AMR) AF: 0.303 AC: 4621 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1227 AN: 3472

East Asian (EAS) AF: 0.150 AC: 777 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1397 AN: 4812

European-Finnish (FIN) AF: 0.482 AC: 5083 AN: 10548

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32077 AN: 67972

Other (OTH) AF: 0.364 AC: 768 AN: 2110

Alfa AF: 0.309 Hom.: 1036

Bravo AF: 0.336

Asia WGS AF: 0.245 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.78
PhyloP100		-0.17
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: rs950643; hg19: chr5-75915905;