Variant rs11706052 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000884.3(IMPDH2):c.819+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,613,738 control chromosomes in the GnomAD database, including 8,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 575 hom., cov: 33)

Exomes 𝑓: 0.099 ( 7640 hom. )

Consequence

IMPDH2
NM_000884.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.998

Variant links:

Genes affected

IMPDH2 (HGNC:6053): (inosine monophosphate dehydrogenase 2) This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

IMPDH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-49026677-A-G is Benign according to our data. Variant chr3-49026677-A-G is described in ClinVar as [Benign]. Clinvar id is 1229935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
IMPDH2	NM_000884.3 linkuse as main transcript	c.819+10T>C	intron_variant	ENST00000326739.9	NP_000875.2
IMPDH2	NM_001410759.1 linkuse as main transcript	c.819+10T>C	intron_variant		NP_001397688.1
IMPDH2	NM_001410760.1 linkuse as main transcript	c.744+10T>C	intron_variant		NP_001397689.1
IMPDH2	NM_001410761.1 linkuse as main transcript	c.744+10T>C	intron_variant		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9 linkuse as main transcript	c.819+10T>C		intron_variant		1	NM_000884.3	ENSP00000321584	P1

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11511

AN:

152158

Hom.:

575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0379

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0824

GnomAD3 exomes

AF:

0.0834

AC:

20969

AN:

251340

Hom.:

1011

AF XY:

0.0840

AC XY:

11410

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.0481

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.0379

Gnomad SAS exome

AF:

0.0569

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0933

GnomAD4 exome

AF:

0.0991

AC:

144841

AN:

1461460

Hom.:

7640

Cov.:

AF XY:

0.0979

AC XY:

71177

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.0510

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.0424

Gnomad4 SAS exome

AF:

0.0578

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0908

GnomAD4 genome

AF:

0.0756

AC:

11512

AN:

152278

Hom.:

575

Cov.:

AF XY:

0.0760

AC XY:

5657

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.0706

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.0382

Gnomad4 SAS

AF:

0.0606

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0819

Alfa

AF:

0.0980

Hom.:

962

Bravo

AF:

0.0694

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 21, 2021	- -

IMPDH2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.4

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over