5-76461731-C-T

Variant names:

• chr5-76461731-C-T
• rs10045155
• NM_006633.5:c.146+62C>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.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. Variant has been reported in ClinVar as (no stars).

• 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
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 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.146+62C>T		intron	N/A	NP_006624.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.146+62C>T		intron	N/A	ENSP00000274364.6
	IQGAP2	ENST00000514350.5	TSL:1	c.65+62C>T		intron	N/A	ENSP00000423672.1
	IQGAP2	ENST00000692467.1		n.409C>T		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.120 AC: 3054 AN: 25554

American (AMR) AF: 0.405 AC: 16849 AN: 41612

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 3902 AN: 22910

East Asian (EAS) AF: 0.525 AC: 19660 AN: 37422

South Asian (SAS) AF: 0.253 AC: 19275 AN: 76078

European-Finnish (FIN) AF: 0.326 AC: 16846 AN: 51738

Middle Eastern (MID) AF: 0.161 AC: 805 AN: 4986

European-Non Finnish (NFE) AF: 0.234 AC: 176439 AN: 753824

Other (OTH) AF: 0.238 AC: 11223 AN: 47088

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

African (AFR) AF: 0.129 AC: 5345 AN: 41490

American (AMR) AF: 0.318 AC: 4854 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2562 AN: 5168

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4812

European-Finnish (FIN) AF: 0.334 AC: 3530 AN: 10560

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16422 AN: 67950

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.239 Hom.: 11603

Bravo AF: 0.230

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.52
PhyloP100		-0.42
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: rs10045155; hg19: chr5-75757556; COSMIC: COSV57172143;