Genetic Variant NM_006633.5:c.1522-4004T>G (chr5-76623406-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006633.5(IQGAP2):c.1522-4004T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 644,724 control chromosomes in the GnomAD database, including 49 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 0.012 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 11 hom. )

Consequence

IQGAP2
NM_006633.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.466

Publications

1 publications found

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]

IQGAP2 links:

F2RL2 (HGNC:3539): (coagulation factor II thrombin receptor like 2) This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]

F2RL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1756/152376) while in subpopulation AFR AF = 0.0404 (1680/41600). AF 95% confidence interval is 0.0388. There are 38 homozygotes in GnomAd4. There are 817 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1756 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP2	NM_006633.5 link	c.1522-4004T>G		intron_variant	Intron 13 of 35	ENST00000274364.11	NP_006624.3	Q13576-1B7Z7U6Q59HA3
F2RL2	NM_004101.4 link	c.-176A>C		upstream_gene_variant		ENST00000296641.5	NP_004092.1	O00254-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP2	ENST00000274364.11 link	c.1522-4004T>G		intron_variant	Intron 13 of 35	1	NM_006633.5	ENSP00000274364.6		Q13576-1
F2RL2	ENST00000296641.5 link	c.-176A>C		upstream_gene_variant		1	NM_004101.4	ENSP00000296641.3		O00254-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1739

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00813

GnomAD4 exome

AF:

0.00139

AC:

683

AN:

492348

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

300

AN XY:

258916

show subpopulations

African (AFR)

AF:

0.0390

AC:

513

AN:

13144

American (AMR)

AF:

0.00294

AC:

AN:

18690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13964

East Asian (EAS)

AF:

0.00

AC:

AN:

31252

South Asian (SAS)

AF:

0.0000217

AC:

AN:

46114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33382

Middle Eastern (MID)

AF:

0.00142

AC:

AN:

2108

European-Non Finnish (NFE)

AF:

0.0000457

AC:

AN:

306424

Other (OTH)

AF:

0.00356

AC:

AN:

27270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0115

AC:

1756

AN:

152376

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

817

AN XY:

74528

show subpopulations

African (AFR)

AF:

0.0404

AC:

1680

AN:

41600

American (AMR)

AF:

0.00366

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68026

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

196

294

392

490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.0132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.3

(source)

DANN

Benign

0.69

PhyloP100

0.47

PromoterAI

-0.20

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over