5-76461731-C-T

Position:

• chr5-76461731-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.146+62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,213,240 control chromosomes in the GnomAD database, including 42,332 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 0.23 (4682 hom., cov: 32)
  • Exomes 𝑓: 0.25 (37650 hom.)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.146+62C>T		intron_variant		ENST00000274364.11	NP_006624.3
IQGAP2	XM_047416641.1	c.221+62C>T		intron_variant			XP_047272597.1
IQGAP2	XM_005248410.4	c.65+62C>T		intron_variant			XP_005248467.1
IQGAP2	XM_017008960.2	c.146+62C>T		intron_variant			XP_016864449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.146+62C>T		intron_variant		1	NM_006633.5	ENSP00000274364.6
IQGAP2	ENST00000514350.5	c.65+62C>T		intron_variant		1		ENSP00000423672.1
IQGAP2	ENST00000692467.1	n.409C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35384 AN: 151910 Hom.: 4680 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.253 AC: 268053 AN: 1061212 Hom.: 37650 AF XY: 0.252 AC XY: 136766 AN XY: 543528

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.525

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.233 AC: 35399 AN: 152028 Hom.: 4682 Cov.: 32 AF XY: 0.240 AC XY: 17830 AN XY: 74336

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.223

Alfa AF: 0.241 Hom.: 8935

Bravo AF: 0.230

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.52

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: rs10045155; hg19: chr5-75757556; COSMIC: COSV57172143;