Menu
GeneBe

5-76461580-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_006633.5(IQGAP2):c.57C>T(p.Asp19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,611,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

IQGAP2
NM_006633.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.319
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-76461580-C-T is Benign according to our data. Variant chr5-76461580-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 723267.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.319 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 43 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IQGAP2NM_006633.5 linkuse as main transcriptc.57C>T p.Asp19= synonymous_variant 2/36 ENST00000274364.11
IQGAP2XM_047416641.1 linkuse as main transcriptc.132C>T p.Asp44= synonymous_variant 2/36
IQGAP2XM_017008960.2 linkuse as main transcriptc.57C>T p.Asp19= synonymous_variant 2/35
IQGAP2XM_005248410.4 linkuse as main transcriptc.-25C>T 5_prime_UTR_variant 2/36

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IQGAP2ENST00000274364.11 linkuse as main transcriptc.57C>T p.Asp19= synonymous_variant 2/361 NM_006633.5 P1Q13576-1
IQGAP2ENST00000514350.5 linkuse as main transcriptc.-25C>T 5_prime_UTR_variant 2/221
IQGAP2ENST00000692467.1 linkuse as main transcriptn.258C>T non_coding_transcript_exon_variant 2/2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000283
AC:
43
AN:
151984
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00125
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000315
AC:
79
AN:
251002
Hom.:
0
AF XY:
0.000310
AC XY:
42
AN XY:
135642
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000753
Gnomad ASJ exome
AF:
0.00338
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000194
AC:
283
AN:
1459924
Hom.:
0
Cov.:
29
AF XY:
0.000198
AC XY:
144
AN XY:
726468
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000761
Gnomad4 ASJ exome
AF:
0.00333
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000102
Gnomad4 OTH exome
AF:
0.000597
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000283
AC:
43
AN:
151984
Hom.:
0
Cov.:
32
AF XY:
0.000216
AC XY:
16
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00125
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000425
Hom.:
0
Bravo
AF:
0.000374
EpiCase
AF:
0.000327
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeFeb 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
Cadd
Benign
0.79
Dann
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372040696; hg19: chr5-75757405; COSMIC: COSV57184276; API