rs3797412

Variant names:

• chr5-76632129-A-C
• rs3797412
• NM_006633.5:c.1780+103A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-76632129-A-C
• chr5-76632129-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006633.5(IQGAP2):​c.1780+103A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 841,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: IQGAP2 NM_006633.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.1780+103A>C		intron	N/A	NP_006624.3	Q13576-1
	IQGAP2	NM_001285460.2		c.1630+103A>C		intron	N/A	NP_001272389.2	F5H7S7
	IQGAP2	NM_001285461.2		c.439+103A>C		intron	N/A	NP_001272390.2	Q13576-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.1780+103A>C		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000396234.7	TSL:1	c.439+103A>C		intron	N/A	ENSP00000379535.3	Q13576-2
	IQGAP2	ENST00000514350.5	TSL:1	c.1699+103A>C		intron	N/A	ENSP00000423672.1	D6R939

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 841932 Hom.: 0 AF XY: 0.00000238 AC XY: 1 AN XY: 420606

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16912

American (AMR) AF: 0.00 AC: 0 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15808

East Asian (EAS) AF: 0.00 AC: 0 AN: 28214

South Asian (SAS) AF: 0.00 AC: 0 AN: 41946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3968

European-Non Finnish (NFE) AF: 0.00000156 AC: 1 AN: 639428

Other (OTH) AF: 0.00 AC: 0 AN: 37342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.84
PhyloP100		-0.58

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: rs3797412; hg19: chr5-75927954;