rs376517879

Variant names:

• chr5-76562544-C-A
• NM_006633.5:c.295C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-76562544-C-A
• chr5-76562544-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006633.5(IQGAP2):​c.295C>A​(p.Arg99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IQGAP2 NM_006633.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP2	NM_006633.5	c.295C>A	p.Arg99Ser	missense_variant	Exon 3 of 36	ENST00000274364.11	NP_006624.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11	c.295C>A	p.Arg99Ser	missense_variant	Exon 3 of 36	1	NM_006633.5	ENSP00000274364.6
IQGAP2	ENST00000514350.5	c.214C>A	p.Arg72Ser	missense_variant	Exon 3 of 22	1		ENSP00000423672.1
IQGAP2	ENST00000379730.7	c.145C>A	p.Arg49Ser	missense_variant	Exon 2 of 35	5		ENSP00000442313.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459764 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D;D;.;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Uncertain	2.7	M;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.8	D;D;D;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.0090	D;D;D;.
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.91
MutPred		0.49		Loss of MoRF binding (P = 0.0318);.;.;.;
MVP		0.96
MPC		0.74
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.72
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-75858369;