chr5-76423003-C-T

Variant names:

• chr5-76423003-C-T
• rs6453220
• NM_006633.5:c.46+19412C>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.46+19412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,174 control chromosomes in the GnomAD database, including 969 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 0.087 (969 hom., cov: 33)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 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.46+19412C>T		intron	N/A	NP_006624.3	Q13576-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.46+19412C>T		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000514350.5	TSL:1	c.-36+18472C>T		intron	N/A	ENSP00000423672.1	D6R939
	IQGAP2	ENST00000692467.1		n.247+19412C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13133 AN: 152056 Hom.: 962 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0878

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

GnomAD4 genome AF: 0.0866 AC: 13174 AN: 152174 Hom.: 969 Cov.: 33 AF XY: 0.0870 AC XY: 6470 AN XY: 74388

African (AFR) AF: 0.194 AC: 8068 AN: 41482

American (AMR) AF: 0.0890 AC: 1361 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.0382 AC: 198 AN: 5188

South Asian (SAS) AF: 0.167 AC: 802 AN: 4810

European-Finnish (FIN) AF: 0.0159 AC: 168 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2121 AN: 68032

Other (OTH) AF: 0.0874 AC: 184 AN: 2106

Alfa AF: 0.0708 Hom.: 125

Bravo AF: 0.0952

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		-0.098
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: rs6453220; hg19: chr5-75718828;