rs6453220

Positions:

• chr5-76423003-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

IQGAP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.46+19412C>T		intron_variant		ENST00000274364.11	NP_006624.3
IQGAP2	XM_047416641.1	c.121+18507C>T		intron_variant			XP_047272597.1
IQGAP2	XM_005248410.4	c.-36+18472C>T		intron_variant			XP_005248467.1
IQGAP2	XM_017008960.2	c.46+19412C>T		intron_variant			XP_016864449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.46+19412C>T		intron_variant		1	NM_006633.5	ENSP00000274364.6
IQGAP2	ENST00000514350.5	c.-36+18472C>T		intron_variant		1		ENSP00000423672.1
IQGAP2	ENST00000692467.1	n.247+19412C>T		intron_variant

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

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0874

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.44

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: rs6453220; hg19: chr5-75718828;